Superficially porous materials comprising a substantially nonporous hybrid core having narrow particle size distribution

ABSTRACT

The present invention provides novel chromatographic materials, e.g., for chromatographic separations, processes for its preparation and separations devices containing the chromatographic material; separations devices, chromatographic columns and kits comprising the same; and methods for the preparation thereof. The chromatographic materials of the invention are chromatographic materials comprising having a narrow particle size distribution.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.13/638,924, filed Feb. 14, 2013, which is the U.S. National Phasepursuant to 35 U.S.C. § 371, of U.S. international application Ser. No.PCT/US2011/045246, filed Jul. 25, 2011, designating the United Statesand published in English on Feb. 9, 2012 as publication WO 2012/018596A2, which claims the benefit of U.S. provisional application Ser. No.61/367,797, filed Jul. 26, 2010. The entire disclosures of each of whichare hereby incorporated herein by this reference.

BACKGROUND OF THE INVENTION

Superficially porous particles (also called pellicular, fused-core, orcore-shell particles) were routinely used as chromatographic sorbents inthe 1970's. These earlier superficially porous materials had thin porouslayers, prepared from the adsorption of silica sols to the surface ofill-defined, polydisperse, nonporous silica cores (>20 μm). The processof spray coating or passing a solution of sols through a bed ofparticles was commonly used. Kirkland extensively explored the use ofsuperficially porous particles throughout this time and helped developthe Zipax brand of superficially porous materials in the 1970's. Areview of Kirkland's career was provided by Unger (Journal ofChromatography A, 1060 (2004) 1).

Superficially porous particles have been a very active area of researchin the past five years. One prior report that uses a mixed condensationof a tetraalkoxysilane with an organosilane of the type YSi(OR)₃ where Ycontains an alkyl or aryl group and R is methoxy or ethoxy, has beenreported by Unger for both fully porous (EP 84,979 B1, 1996) andsuperficially porous particles (Advanced Materials 1998, 10, 1036).These particles do not have sufficient size (1-2 μm) for effective usein UPLC, nor do they contain chromatographically enhanced pore geometry.Narrow distribution superficially porous particles have been reported byKirkland (US Application 20070189944) using a Layer-by-Layer approach(LBL)—however these particles are not highly spherical. Othersurfactant-templated approaches, can yield low yields of narrowdistribution, fully porous particles, however these approaches have notbeen used to prepare monodisperse, spherical superficially porousparticles having chromatographically enhanced pore geometry.

Modern, commercially available superficially porous particles usesmaller (<2 μm), monodisperse, spherical, high purity non-porous silicacores. A porous layer is formed, growing these particles to a finaldiameter between 1.7-2.7 μm. The thickness of the porous layer and porediameter are optimized to suit a particular application (e.g., small vs.large molecule separations). In order to remove polyelectrolytes,surfactants, or binders (additional reagents added during the synthesis)and to strengthen the particles for use in HPLC or UPLC applications,these material are calcined (500-1000° C. in air). Additional poreenlargement, acid treatment, rehydroxylation, and bonding steps havebeen reported.

Evaluation of superficially porous materials (e.g., Journal ofChromatography A, 1217 (2010) 1604-1615; Journal of Chromatography A,1217 (2010) 1589-1603) indicates improvements in column performance maybe achieved using columns packed with these superficially porousmaterials. While not limited to theory, improvements were noted in vanDeemter terms as well as improved thermal conductivity. The Universityof Cork also has a recent patent application (WO 2010/061367 A2) onsuperficially porous particles.

Although these reported superficially porous particle processes differ,they can be classified as layering of preformed sols (e.g., AMT process)or growth using high purity tetraalkoxysilane monomers (e.g., theUniversity of Cork process). The AMT and University of Cork processesare similar in that they incorporate a repeated in-process workup (overnine times) using centrifugation followed by redispersion. For the AMTprocess this is a requirement of the layer-by-layer approach, in whichalternate layers of positively charged poly-electrolyte and negativelycharged silica sols are applied. For the University of Cork process thein-process workup is used to reduce reseeding and agglomeration events.Particles prepared by this approach have smooth particle surfaces andhave notable layer formation by FIB/SEM analysis. While both approachesuse similar spherical monodisperse silica cores that increase inparticle size as the porous layer increases, they differ in finalparticle morphology of the superficially porous particle. The AMTprocess, as shown in FIG. 8, results in bumpy surface features andvariation of the porous layer thickness. This difference in surfacemorphology may be due to variation in the initial layering of sols. Mostnotably both processes use high temperature thermal treatment in air toremove additives (polyelectrolyte or surfactants) and improve themechanical properties of their superficially porous particles. Sincehybrid materials are not thermally stable above 600° C., this approachis not applicable to the formation of hybrid superficially porousparticles.

The synthesis of narrow particle size distribution porouschromatographic particles is expected to have great benefit forchromatographic separations. Such particles should have an optimalbalance of column efficiency and backpressure. While the description ofmonodisperse superficially porous silica particles has been noted in theliterature, these particles do not display chromatographically enhancedpore geometry and desirable pore diameters for many chromatographicapplications. Thus, there remains a need for a process in which narrowparticle size distribution porous materials can be prepared withdesirable pore diameters and chromatographically enhanced pore geometry.Similarly, there remains a need for a process in which narrow particlesize distribution porous materials can be prepared with improvedchemical stability with high pH mobile phases.

BRIEF SUMMARY OF THE INVENTION

In one aspect, the invention provides a superficially porous materialcomprising a substantially nonporous inorganic/organic hybrid core andone or more layers of a porous shell material surrounding the core.

In certain embodiments, the material of the invention is comprised ofsuperficially porous particles. In other embodiments the material of theinvention is comprised of a superficially porous monolith.

In certain embodiments, the material of the invention has asubstantially narrow particle size distribution. In particularembodiments the 90/10 ratio of particle sizes of the material is from1.00-1.55; from 1.00-1.10 or from 1.05-1.10. In specific embodiments,the core has a substantially narrow particle size distribution. Inparticular embodiments the 90/10 ratio of particle sizes of the core isfrom 1.00-1.55; from 1.00-1.10 or from 1.05-1.10.

In certain embodiments, the material of the invention haschromatographically enchancing pore geometry.

In other embodiments, the material of the invention has a smallpopulation of micropores.

In certain embodiments, the material of the invention comprises a hybridcore having the formula:(SiO₂)_(d)/[R²((R)_(p)(R¹)_(q)SiO_(t))_(m)]  (I)wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

p and q are each independently 0.0 to 3.0,

t is 0.5, 1.0, or 1.5;

d is 0 to about 30;

m is an integer from 1-20; wherein R, R¹ and R² are optionallysubstituted; provided that: (1) when R² is absent, m=1 and

${t = \frac{\left( {4 - \left( {p + q} \right)} \right)}{2}},$when 0<p+q≤3; and

-   -   (2) when R² is present, m=2-20 and

${t = \frac{\left( {3 - \left( {p + q} \right)} \right)}{2}},$when p+q≤2.

In other embodiments, the material of the invention comprises a hybridcore having the formula:(SiO₂)_(d)/[(R)_(p)(R¹)_(q)SiO_(t)]  (II)wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

d is 0 to about 30;

p and q are each independently 0.0 to 3.0, provided that when p+q=1 thent=1.5; when p+q=² then t=1; or when p+q=3 then t=0.5.

In yet other embodiments, the material of the invention comprises ahybrid core having has the formula:(SiO₂)d/[R²((R¹)_(r)SiO_(t))_(m)]  (III)wherein,

R¹ is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

d is 0 to about 30;

r is 0, 1 or 2, provided that when r=0 then t=1.5; when r=1 then t=1; orwhen r=2, then t=0.5; and

m is an integer from 1-20.

In still other embodiments, the material of the invention comprises ahybrid core having the formula:(A)_(x)(B)_(y)(C)_(z)  (IV)wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block; A is an organic repeat unit which iscovalently bonded to one or more repeat units A or B via an organicbond; B is an organosiloxane repeat unit which is bonded to one or morerepeat units B or C via an inorganic siloxane bond and which may befurther bonded to one or more repeat units A or B via an organic bond; Cis an inorganic repeat unit which is bonded to one or more repeat unitsB or C via an inorganic bond; x and y are positive numbers, and z is anon negative number, wherein x+y+z=1. In certain embodiments, z=0, then0.002≤x/y≤210, and when z≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In other embodiments, the material of the invention comprises a hybridcore having the formula:(A)_(x)(B)_(y)(B*)_(y*)(C)_(z)  (V)wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block; A is an organic repeat unit whichis covalently bonded to one or more repeat units A or B via an organicbond; B is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond, B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization; C is aninorganic repeat unit which is bonded to one or more repeat units B orB* or C via an inorganic bond; x and y are positive numbers and z is anon negative number, wherein x+y+z=1. In certain embodiments, when z=0,then 0.002≤x/(y+y*)≤210, and when z≠0, then 0.0003≤(y+y*)/z≤500 and0.002≤x/(y+y*+z)≤210.

In certain embodiments, the porous shell material is a porous silica.

In other embodiments, the porous shell material is a porous compositematerial.

In certain embodiments, in which the material of the invention comprisesmore than one layer of porous shell material, each layer isindependently selected from is a porous inorganic/organic hybridmaterial, a porous silica, a porous composite material or mixturesthereof.

In certain embodiments, the hybrid core of the material of the inventionhas an increased hybrid content near the surface of the core.

In other embodiments, the hybrid core of the material of the inventionhas a decreased hybrid content near the surface of the core.

In certain embodiments, the material of the invention has an increasedhybrid content near the surface of the superficially porous material.

In other embodiments, the material of the invention has a decreasedhybrid content near the surface of the superficially porous material.

In certain embodiments, the material of the invention has a highlyspherical core morphology; a rod shaped core morphology; a bent-rodshaped core morphology; a toroid shaped core morphology; or a dumbbellshaped core morphology.

In particular embodiments, the material of the invention has a mixtureof highly spherical, rod shaped, bent-rod shaped, toroid shaped ordumbbell shaped core morphologies.

In particular embodiments, the material of the invention has asignificantly higher thermal conductivity than a fully porous silicaparticles of the same size. In other embodiments, the material of theinvention has a significantly higher thermal conductivity than asuperficially porous silica particles of the same size.

In particular embodiments, the material of the invention are capable offorming a packed beds with improved permeability as compared to a fullyporous silica particles of the same size.

In still other embodiments, the material of the invention is capable offorming a packed beds with improved permeability as compared to asuperficially porous silica particles of the same size.

In particular embodiments, the material of the invention has improvedchemical stability to high pH mobile phases as compared to unbonded,fully porous silica particles of the same size. In still otherembodiments, the material of the invention improved chemical stabilityto high pH mobile phases as compared to unbonded, superficially poroussilica particles of the same size.

In certain embodiments, the core has a particle size of 0.5-10 μm;0.8-5.0 μm; or 1.3-3.0 μm.

In other embodiments, each porous layer is independently from 0.05 μm to5 μm. in thickness as measured perpendicular to the surface of thenonporous core; from 0.06 μm to 1 μm. in thickness as measuredperpendicular to the surface of the nonporous core; or from 0.20 μm to0.70 μm. in thickness as measured perpendicular to the surface of thenonporous core.

In particular embodiments, the materials of the invention have anaverage particle size between 0.8-10.0 Mm; between 1.1-5.0 Mm; orbetween 1.3-2.9 μm.

In other embodiments, the materials of the invention have pores havingan average diameter of about 25-600 Å; about 60-350 Å; about 80-300 Å;or about 90-150 Å.

In still other embodiments, the materials of the invention have anaverage pore volume of about 0.11-0.50 cm³/g; of about 0.09-0.45 cm³/g;or of about 0.17-0.30 cm³/g.

In yet other embodiments, the materials of the invention have a poresurface area is between about 10 m²/g and 400 m²/g; between about 15m²/g and 300 m²/g; or between about 60 m²/g and 200 m²/g.

In still other embodiments, the materials of the invention are surfacemodified. In particular embodiments, the materials of the invention aresurface modified by: coating with a polymer;

-   -   by coating with a polymer by a combination of organic group and        silanol group modification;    -   a combination of organic group modification and coating with a        polymer;    -   a combination of silanol group modification and coating with a        polymer;    -   formation of an organic covalent bond between the material's        organic group and a modifying reagent; or    -   a combination of organic group modification, silanol group        modification and coating with a polymer.

In certain embodiments of the invention, the superficially porousmaterial has a smooth surface. In other embodiments of the invention,the superficially porous material has a rough surface.

In another aspect, the invention provides a method for preparing asuperficially porous material comprising:

-   -   a.) providing a substantially nonporous hybrid core material;        and    -   b.) applying to said core material one or more layers of porous        shell material to form a superficially porous material

In certain embodiments, the method for preparing a superficially porousmaterial further comprises the step of:

-   -   c.) optimizing one or more properties of the superficially        porous material.

In other embodiments, each layer of porous shell material wherein eachlayer is independently selected from is a porous inorganic/organichybrid material, a porous silica, a porous composite material ormixtures thereof.

In still other embodiments, each layer of porous shell material isapplied using sols, a polyelectrolyte or a chemically degradablepolymer, wherein:

a) the sols are inorganic sols, hybrid sols, nanoparticles, or mixturesthereof; and

b) the polyelectrolyte or chemically degradable polymer is removed fromthe material using chemical extraction, degradation, or thermaltreatment at temperatures less than 500° C., or combinations thereof.

In certain embodiments, each layer of porous shell material is appliedby formation through an electrostatic or acid/base interaction of anionizable group comprising the steps of:

-   -   a) prebonding the substantially nonporous core with an        alkoxysilane that has an ionizable group,    -   b) treating the substantially nonporous core to sols that are        inorganic, hybrid, nanoparticle, or mixtures thereof, that have        been prebonded with an alkoxysilane that has an ionizable group        of the opposite charge to the ionizable group on the surface of        the core; and    -   c) forming additional layers on the material with sols that are        inorganic, hybrid, nanoparticle, or mixtures thereof that have        been prebonded with an alkoxysilane that has an ionizable group        of opposite charge to the ionizable group of prior layer.

In particular embodiments, the prebonding of the substantially nonporouscore or sols includes washing with and acid or base, or a chargedpolyelectrolyte. In other embodiments, the prebonding of thesubstantially nonporous core or sols includes chemical transformation ofan accessible hybrid organic group.

In still other embodiments the accessible hybrid organic group is anaromatic group that can undergo sulfonation, nitration, amination, orchloromethylation followed by oxidation or nucleophillic displacementwith amine containing groups to form ionizable groups. In yet otherembodiments, the accessible hybrid organic group is an alkene group thatcan undergo oxidation, cross-metathesis, or polymerization to formionizable groups. In specific embodiments, the accessible hybrid organicgroup is a thiol group that can undergo oxidation, radical addition,nucleophillic displacement, or polymerization to form ionizable groups.

In yet other embodiments, the prebonding of the substantially nonporouscore or sols includes bonding with an alkoxysilane that has an ionizablegroup of equation 1,R(CH₂)_(n)Si(Y)_(3-x)(R′)_(x)  (equation 1)where n=1-30, advantageously 2-3;x is 0-3; advantageously 0;Y represents chlorine, dimethylamino, triflate, methoxy, ethoxy, or alonger chain alkoxy group;R represent a basic group, including (but not limited to) —NH₂, —N(R′)H,—N(R′)₂, —N(R′)₃ ⁺, —NH(CH₂)_(m)NH₂, —NH(CH₂)_(m)N(R′)H,—NH(CH₂)_(m)N(R′)₂, —NH(CH₂)_(m)N(R′)₃ ⁺, pyridyl, imidizoyl, polyaminc.R¹ independently represents an alkyl, branched alkyl, aryl, orcycloalkyl group; m is 2-6.

In still yet other embodiments, the prebonding of the substantiallynonporous core or sols includes bonding with an alkoxysilane that has anionizable group of equation 2,A(CH₂)_(n)Si(Y)_(3-x)(R′)_(x)  (equation 2)where n=1-30, advantageously 2-3;x is 0-3; advantageously 0;Y represents chlorine, dimethylamino, triflate, methoxy, ethoxy, or alonger chain alkoxy group;A represent an acidic group, including (but not limited to) a sulfonicacid, carboxylic acid, phosphoric acid, boronic acid, arylsulfonic acid,arylcarboxylic acid, arylphosphonic acid, and arylboronic acid.R¹ independently represents an alkyl, branched alkyl, aryl, orcycloalkyl group.

In particular embodiments, each layer of porous shell material isapplied using a polyelectrolyte or a chemically degradable polymer.

In other embodiments, the polyelectrolyte or a chemically degradable isremoved from the material by chemical extraction, degradation, orthermal treatment at temperatures less than 500° C., or combinationsthereof.

In certain embodiments, each layer of porous shell material is appliedusing alkoxysilanes, organoalkoxysilanes, nanoparticles,polyorganoalkoxysiloxanes, or combinations thereof, comprising the stepsof:

-   -   a) condensing siloxane precursors on the substantially nonporous        core in a reaction mixture comprising ethanol, water and        ammonium hydroxide and optionally containing a non-ionic        surfactant, an ionic surfactant, a polyelectrolyte or a polymer        to form the porous shell material; and    -   b) introducing porosity is introduced through extraction,        degradation, oxidation, hydrolysis, deprotection, or        transformation of the hybrid group, ionic surfactant or        non-ionic surfactant or a combination thereof.

In particular embodiments, the alkoxysilanes, organoalkoxysilanes,nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof, arecondensed on the substantially nonporous core in a solution comprisingethanol, water, ammonium hydroxide, an ionic surfactant; and annon-ionic surfactant.

In other embodiments, the ionic surfactant is C₁₀-C₃₀N(R)₃ ⁺X⁻, where Ris methyl, ethyl, propyl, alkyl, fluoroalkyl; X is a halogen, hydroxide,or of the form R′SO₃ ⁻ or R′CO₂ ⁻ where R′ is methyl, ethyl, butyl,propyl, isopropyl, tert-butyl, aryl, tolyl, a haloalkyl or a fluoroalkylgroup.

In yet other embodiments, the ionic surfactant isoctadecyltrimethylammonium bromide, octadecyltrimethylammonium chloride,hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride,dodecyltrimethylammonium bromide, or dodecyltrimethylammonium chloride.

In particular embodiments, the concentration of ionic surfactant ismaintained in the reaction solution between 5-17 mM; or in certainembodiments between 8-14 mM.

In other embodiments, the non-ionic surfactant is a diblock or triblockcopolymer. In certain embodiments, the copolymer is (PEO)x(PPO)y(PEO)x,wherein

PEO is a polyethylene oxide repeat unit,

PPO is a polypropylene oxide repeat unit,

x is an integer between 5-106,

y is an integer between 30-85.

In particular embodiments the triblock copolymer is Pluronic® P123,having (PEO)₂₀(PPO)₇₀(PEO)₂₀. In still other embodiments, thealkoxysilanes, organoalkoxysilanes, or combinations thereof, arecondensed on the substantially nonporous core in a solution comprising:

ethanol, water, ammonium hydroxide or combinations thereof;

ocladecyltrimethylammonium bromide; and Pluronic® P123.

In certain embodiments, the alkoxysilane used is selected from the groupof tetramethoxsilane or tetraethoxysilane.

In still other embodiments, the organosiloxane is selected from thegroup of phenyltriethoxysilane; phenyltrimethoxysilane;phenylethyltriethoxysilane; phenylethyltrimethoxysilane;ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane;methyltrimethoxysilanc, diethyldicthoxysilane; dicthyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(trimethoxysilyl)ethane; 2-bis(triethoxysilyl)ethane;1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane;vinyltriethoxysilane; vinyltrimethoxysilane;mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane;1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene;1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane;1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(tricthoxysilylethyl)benzene; or1,3-bis(trimethoxysilylethyl)benzene.

In yet other embodiments, the alkoxysilane used is tetraethoxysilane andthe organoalkoxysilane used is 1,2-bis(triethoxysilyl)ethane.

In certain other embodiments, the concentration ofoctadecyltrimethylammonium bromide is maintained between 8-14 mM.

In certain other embodiments, the molar ratio ofoctadecyltrimethylammonium bromide and Pluronic® P123 is maintained ator above 1.30.

In still other embodiments, the molar ratio of alkoxysilane toorganoalkoxysilane ranges between 30:1 to 1:30.

In certain embodiments, alkoxysilane, organoalkoxysilane, orcombinations thereof are prediluted in ethanol. In certain suchembodiments, prediluted ethanol solutions of alkoxysilane,organoalkoxysilane, or combinations thereof are added at a slow andconstant rate to prevent fines generation, aggregation andagglomeration. In other such embodiments, prediluted ethanol solutionsof alkoxysilane, organoalkoxysilane, or combinations thereof are added arate between 5-500 μL/min.

In other embodiments, a secondary solution comprising ethanol, water,ammonium hydroxide, ionic surfactant and non-ionic surfactant is addedat a slow and constant rate to prevent fines generation, aggregation andagglomeration. In certain such embodiments the secondary solutioncomprising ethanol, water, ammonium hydroxide, ionic surfactant andnon-ionic surfactant is added within a range between the rate requiredto maintain a uniform ratio of particle surface area (m²) to reactionvolume, to the rate required to maintain a uniform ratio of particlevolume (m³) to reaction volume.

In certain embodiments, the surfactant mixture is removed through one ormore of the following; extractions with acid, water, or organic solvent;ozonolysis treatments, thermal treatments <500° C., or thermaltreatments between 500-1000° C.

In still other embodiments, the surfactant mixture is removed throughcombination of acid extractions and ozonolysis treatments.

In certain embodiments, each layer of porous shell material is appliedusing alkoxysilanes, organoalkoxysilanes, nanoparticles,polyorganoalkoxysiloxanes, or combinations thereof: comprising the stepsof:

-   -   a) condensing siloxane precursors on the substantially        nonporoous core in a reaction mixture comprising ethanol, water        or ammonium hydroxide to form a non-porous hybrid        inorganic/organic shell material; and    -   b) introducing porosity is introduced through extraction,        degradation, oxidation, hydrolysis, deprotection, or        transformation of the hybrid group or a combination thereof.

In some such embodiments, the alkoxysilane used is selected from thegroup of tetramethoxsilane or tetraethoxysilane.

In other such embodiments, the organosiloxane is selected as one or moreof the following from the group of phenyltriethoxysilane;phenyltrimethoxysilane; phenylethyltriethoxysilane;phenylethyltrimethoxysilane; ethyltriethoxysilane;ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane,diethyldiethoxysilane; diethyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(trimethoxysilyl)ethane; 1,2-bis(triethoxysilyl)ethane;1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane;vinyltriethoxysilane; vinyltrimethoxysilane;mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane;1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene;1,1-bis(tricthoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane;1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(triethoxysilylethyl)benzene; or1,3-bis(trimethoxysilylethyl)benzene, octadecyltrimethoxysilane,octadecyltriethoxysilane, octyltrimethoxysilane, octyltriethoxysilane,dodecyltrimethoxysilane, and dodecyltriethoxysilane.

In still other such embodiments, the alkoxysilane used istetraethoxysilane and the organoalkoxysilane used isoctadecyltrimethoxysilane.

In certain such embodiments, the alkoxysilane, one or moreorganoalkoxysilanes, or combinations thereof are prediluted in ethanol.

In some such embodiments, the prediluted ethanol solutions ofalkoxysilane, one or more organoalkoxysilanse, or combinations thereofare added a slow and constant rate to prevent fines generation,aggregation and agglomeration.

In other such embodiments, prediluted ethanol solutions of alkoxysilane,one or more organoalkoxysilanes, or combinations thereof are added arate between 5-500 μL/min.

In certain embodiments, a secondary solution comprising ethanol, water,and ammonium hydroxide is added at a slow and constant rate to preventfines generation, aggregation and agglomeration.

In certain other embodiments, a secondary solution comprising ethanol,water, and ammonium hydroxide is added within a range between the raterequired to maintain a uniform ratio of particle surface area (m²) toreaction volume, to the rate required to maintain a uniform ratio ofparticle volume (m³) to reaction volume.

In certain embodiments, porosity is introduced through extraction,degradation, hydrolysis, deprotection, or transformation of the hybridgroup through one or more of the following; extractions with acid,water, or organic solvent; ozonolysis treatments, thermal treatments<500° C., or thermal treatments between 500-1000° C.

In still other embodiments, porosity is introduced through extraction,degradation, hydrolysis, deprotection, or transformation of the hybridgroup through combination of acid extractions, ozonolysis treatmentsand/or thermal treatments <500° C.

In certain embodiments, each layer is applied using a mixture of formulaXX.(D)_(d)(E)_(e)(F)_(f)  (Formula XX)wherein,

a) d+e+f=1,

b) D is one or more inorganic components upon initial condensation,

c) E is one or more hybrid components upon initial condensation and

d) F is one or more hybrid components upon initial condensation that canbe further reacted to increase the porosity of the superficially porouslayer In certain such embodiments, the precursor for the inorganiccomponent upon initial condensation (D) is selected from oxide,hydroxide, ethoxide, methoxide, propoxide, isopropoxide, butoxide,sec-butoxide, tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide,2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate,nitrate, chlorides, and mixtures thereof of silicon, titanium,zirconium, or aluminum.

In other such embodiments, the precursor for the inorganic componentupon initial condensation (D) is selected from tetraethoxysilane,tetramethoxysilane, methyl titanium triisopropoxide, methyl titaniumtriphenoxide, titanium allylacetoacetatetriisopropoxide, titaniummnethacrylate triisopropoxide, titanium methacryloxyethylacetoacetatetriisopropoxide, pentamethylcyclopentadienyl titanium trimethoxide,pentamethylcyclopentadienyl titanium trichloride, and zirconiummethacryloxyethylacetoacetate tri-n-propoxide.

In still other such embodiments, the precursor for the hybrid componentupon initial condensation (E) is selected from1,2-bis(triethoxysilyl)ethane, 1,2-bis(trimethoxysilyl)ethane,1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene,1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene,1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene,and bis(4-triethoxysilylphenyl)diethoxysilane.

In yet other such embodiments, the precursor for the hybrid componentupon initial condensation that can be further reacted to increase theporosity of the superficially porous layer (F) is selected fromphenyltrimethoxysilane, phenyltriethoxysilane,acetyloxyethyltrimethoxysilane; acetyloxyethyltriethoxysilane;chloroethyltriethoxysilane; chloroethyltrimethoxysilane;methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane;bromoethyltrimethoxysilane; bromoethyltriethoxysilane;fluorotriethoxysilane; fluorotrimethoxysilane; and alkoxysilanes of thetype:(CH₃CH₂O)_(4-v)Si(OR*)_(v)  (Formula XXb)wherein

R* was the corresponding octadecyl, dodecyl, octyl, 2-ethoxyethyl, or3-ethyl-3-pentyl group,

v was an integer equal to 1-4,

In such embodiments, porosity is introduced by reaction of hybrid groupF through protodesilylation, hydrolysis, deprotection, acid extraction,thermal treatment <500° C., oxidation, ozonolysis or decomposition.

Another aspect of the invention provides, a method to produce a hybridcore with increased hybrid content near the surface of the core bymodifying a nonporous silica core with one more or more layers formedusing an organosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

Still another aspect of the invention provides, a method to produce asuperficially porous hybrid material that has increased hybrid contentnear the external surface of the material by modifying a superficiallyporous material with one more or more layers formed using anorganosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

Yet another aspect of the invention provides, a method to produce asuperficially porous hybrid particle that has increased hybrid contentnear the external surface of the particle by modifying a superficiallyporous particle with one more or more layers formed using anorganosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

Still another aspect of the invention provides, a method to produce asuperficially porous hybrid particle that has increased hybrid contentnear the external surface of the particle by modifying a superficiallyporous particle that is substantially silica (>90 molar %) with one moreor more layers formed using an organosiloxane, a mixture oforganosiloxane and alkoxysilane, polyorganoalkoxysilanes, a hybridinorganic/organic surrounding material, or combination thereof.

Still yet another aspect of the invention provides, a method to producea superficially porous hybrid particle that has increased hybrid contentnear the external surface of the particle comprising the steps of

a.) forming a superficially porous particle that is substantially silica(>90 molar %) and has a pore volume between 0.18-0.50 cm³/g; and

b.) reducing the porosity of this particle by 0.01-0.20 cm³/g bymodifying this particle with one more or more layers formed using anorganosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

In certain embodiments of the invention, the methods provide materialsin which 1-15 layers are formed in the process. In other aspects, 2-5layers are formed. In still other 1-2 layers are formed.

In certain embodiments of the invention the superficially porousmaterial is optimized by acid extraction, classification, ozonolysistreatment, hydrothermal treatment, acid treatment or combinationsthereof.

In yet other embodiments of the invention, the superficially porousmaterial is further surface modified. In some aspects by: coating with apolymer; coating with a polymer by a combination of organic group andsilanol group modification; a combination of organic group modificationand coating with a polymer; a combination of silanol group modificationand coating with a polymer; formation of an organic covalent bondbetween the material's organic group and a modifying reagent; or acombination of organic group modification, silanol group modificationand coating with a polymer.

In another aspect, the invention provides a method for increasing theporosity of a substantially nonporous material comprising:

-   -   a.) providing a substantially nonporous hybrid core material;        and    -   b.) applying to said core material one or more layers of porous        shell material to form a superficially porous material.

In another aspect, the invention provides a separations device having astationary phase comprising the superficially porous material of theinvention. In certain embodiments, said device is selected from thegroup consisting of chromatographic columns, thin layer plates,filtration membranes, microfluidic separation devices, sample cleanupdevices, solid supports, solid phase extraction devices, microchipseparation devices, and microtiter plates.

In certain other embodiments, the separations device is useful forapplications selected from the group consisting of solid phaseextraction, high pressure liquid chromatography, ultra high pressureliquid chromatography, combinatorial chemistry, synthesis, biologicalassays, ultra performance liquid chromatography, ultra fast liquidchromatography, ultra high pressure liquid chromatography, supercriticalfluid chromatography, and mass spectrometry. In still other embodiments,the separations device is useful for biological assays and wherein thebiological assays are affinity assays or ion-exchanged assays.

In another aspect, the invention provides a chromatographic column,comprising

a) a column having a cylindrical interior for accepting a packingmaterial and

b) a packed chromatographic bed comprising the superficially porousmaterial of the invention.

In another aspect, the invention provides a chromatographic device,comprising

a) an interior channel for accepting a packing material and

b) a packed chromatographic bed comprising the superficially porousmaterial of the invention.

In another aspect, the invention provides a kit comprising thesuperficially porous material of the invention, and instructions foruse. In certain embodiments, the instructions are for use with aseparations device. In certain other embodiments, the separations deviceis selected from the group consisting of chromatographic columns, thinlayer plates, microfluidic separation devices, solid phase extractiondevices, filtration membranes, sample cleanup devices and microtiterplates.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an SEM analysis of Products 1h (top) and 1l (bottom) fromExample 1.

FIG. 2 is an SEM analysis of Products 5a from Example 5.

FIG. 3 is an SEM analysis of Products 11b from Example 11.

FIG. 4 is an SEM analysis of Products diamond cores (top) and Product73L1(bottom) from Example 73.

FIG. 5 is an SEM analysis of Products 74L3 from Example 74.

FIG. 6 is an SEM analysis of Products 76L2 (top) and 77L2 (bottom) fromExamples 76 and 77.

FIG. 7 is an SEM (left) and FIB/SEM (middle, right) analysis of selectedsuperficially porous particles from Example 44.

FIG. 8 is an SEM left) and FIB/SEM analysis of HALO (AMT) Superficiallyporous particles.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides novel chromatographic materials, e.g.,for chromatographic separations, processes for its preparation andseparations devices containing the chromatographic material. The presentinvention will be more fully illustrated by reference to the definitionsset forth below.

Definitions

“Hybrid”, including “hybrid inorganic/organic material,” includesinorganic-based structures wherein an organic functionality is integralto both the internal or “skeletal” inorganic structure as well as thehybrid material surface. The inorganic portion of the hybrid materialmay be, e.g., alumina, silica, titanium, cerium, or “Hybrid” includesinorganic-based structures wherein an organic functionality is integralto both the internal or “skeletal” inorganic structure as well as thehybrid material surface. The inorganic portion of the hybrid materialmay be, e.g., alumina, silica, titanium, cerium, or zirconium oxides, orceramic material; in an advantageous embodiment, the inorganic portionof the hybrid material is silica. As noted above, exemplary hybridmaterials are shown in U.S. Pat. Nos. 4,017,528, 6,528,167, 6,686,035and 7,175,913 and International Application Publication No.WO2008/103423.

The term “alicyclic group” includes closed ring structures of three ormore carbon atoms. Alicyclic groups include cycloparaffins or naphtheneswhich are saturated cyclic hydrocarbons, cycloolefins, which areunsaturated with two or more double bonds, and cycloacetylenes whichhave a triple bond. They do not include aromatic groups. Examples ofcycloparaffins include cyclopropane, cyclohexane and cyclopentane.Examples of cycloolefins include cyclopentadiene and cyclooctatetraene.Alicyclic groups also include fused ring structures and substitutedalicyclic groups such as alkyl substituted alicyclic groups. In theinstance of the alicyclics such substituents can further comprise alower alkyl, a lower alkenyl, a lower alkoxy, a lower alkylthio, a loweralkylamnino, a lower alkylcarboxyl, a nitro, a hydroxyl, —CF₃, —CN, orthe like.

The term “aliphatic group” includes organic compounds characterized bystraight or branched chains, typically having between 1 and 22 carbonatoms. Aliphatic groups include alkyl groups, alkenyl groups and alkynylgroups. In complex structures, the chains can be branched orcross-linked. Alkyl groups include saturated hydrocarbons having one ormore carbon atoms, including straight-chain alkyl groups andbranched-chain alkyl groups. Such hydrocarbon moieties may besubstituted on one or more carbons with, for example, a halogen, ahydroxyl, a thiol, an amino, an alkoxy, an alkylcarboxy, an alkylthio,or a nitro group. Unless the number of carbons is otherwise specified,“lower aliphatic” as used herein means an aliphatic group, as definedabove (e.g., lower alkyl, lower alkenyl, lower alkynyl), but having fromone to six carbon atoms. Representative of such lower aliphatic groups,e.g., lower alkyl groups, are methyl, ethyl, n-propyl, isopropyl,2-chloropropyl, n-butyl, sec-butyl, 2-aminobutyl, isobutyl, tert-butyl,3-thiopentyl and the like. As used herein, the term “nitro” means —NO2;the term “halogen” designates —F, —Cl, —Br or —I; the term “thiol” meansSH; and the term “hydroxyl” means —OH. Thus, the term “alkylamino” asused herein means an alkyl group, as defined above, having an aminogroup attached thereto. Suitable alkylamino groups include groups having1 to about 12 carbon atoms, advantageously from 1 to about 6 carbonatoms. The term “alkylthio” refers to an alkyl group, as defined above,having a sulfhydryl group attached thereto. Suitable alkylthio groupsinclude groups having 1 to about 12 carbon atoms, advantageously from 1to about 6 carbon atoms. The term “alkylcarboxyl” as used herein meansan alkyl group, as defined above, having a carboxyl group attachedthereto. The term “alkoxy” as used herein means an alkyl group, asdefined above, having an oxygen atom attached thereto. Representativealkoxy groups include groups having 1 to about 12 carbon atoms,advantageously 1 to about 6 carbon atoms, e.g., methoxy, ethoxy,propoxy, tert-butoxy and the like. The terms “alkenyl” and “alkynyl”refer to unsaturated aliphatic groups analogous to alkyls, but whichcontain at least one double or triple bond respectively. Suitablealkenyl and alkynyl groups include groups having 2 to about 12 carbonatoms, advantageously from 1 to about 6 carbon atoms.

The term “alkyl” includes saturated aliphatic groups, includingstraight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl(alicyclic) groups, alkyl substituted cycloalkyl groups and cycloalkylsubstituted alkyl groups. In certain embodiments, a straight chain orbranched chain alkyl has 30 or fewer carbon atoms in its backbone, e.g.,C1-C30 for straight chain or C3-C30 for branched chain. In certainembodiments, a straight chain or branched chain alkyl has 20 or fewercarbon atoms in its backbone, e.g., C1-C20 for straight chain or C3-C20for branched chain, and more advantageously 18 or fewer. Likewise,advantageous cycloalkyls have from 4-10 carbon atoms in their ringstructure and more advantageously have 4-7 carbon atoms in the ringstructure. The term “lower alkyl” refers to alkyl groups having from 1to 6 carbons in the chain and to cycloalkyls having from 3 to 6 carbonsin the ring structure.

Moreover, the term “alkyl” (including “lower alkyl”) as used throughoutthe specification and Claims includes both “unsubstituted alkyls” and“substituted alkyls”, the latter of which refers to alkyl moietieshaving substituents replacing a hydrogen on one or more carbons of thehydrocarbon backbone. Such substituents can include, for example,halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy,aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl,aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato,phosphinato, cyano, amino (including alkyl amino, dialkylamino,arylamino, diarylamino and alkylarylamino), acylamino (includingalkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino,imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfate,sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido,heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. It willbe understood by those skilled in the art that the moieties substitutedon the hydrocarbon chain can themselves be substituted, if appropriate.Cycloalkyls can be further substituted, e.g., with the substituentsdescribed above. An “aralkyl” moiety is an alkyl substituted with anaryl, e.g., having 1 to 3 separate or fused rings and from 6 to about 18carbon ring atoms, e.g., phenylmethyl (benzyl).

The term “amino,” as used herein, refers to an unsubstituted orsubstituted moiety of the formula —NRaRb, in which Ra and Rb are eachindependently hydrogen, alkyl, aryl, or heterocyclyl, or Ra and Rb,taken together with the nitrogen atom to which they are attached, form acyclic moiety having from 3 to 8 atoms in the ring. Thus, the term“amino” includes cyclic amino moieties such as piperidinyl orpyrrolidinyl groups, unless otherwise stated. An “amino-substitutedamino group” refers to an amino group in which at least one of Ra andRb, is further substituted with an amino group.

The term “aromatic group” includes unsaturated cyclic hydrocarbonscontaining one or more rings. Aromatic groups include 5- and 6-memberedsingle-ring groups which may include from zero to four heteroatoms, forexample, benzene, pyrrole, furan, thiophene, imidazole, oxazole,thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine andpyrimidine and the like.

The aromatic ring may be substituted at one or more ring positions with,for example, a halogen, a lower alkyl, a lower alkenyl, a lower alkoxy,a lower alkylthio, a lower alkylamino, a lower alkylcarboxyl, a nitro, ahydroxyl, —CF3, —CN, or the like.

The term “aryl” includes 5- and 6-membered single-ring aromatic groupsthat may include from zero to four heteroatoms, for example,unsubstituted or substituted benzene, pyrrole, furan, thiophene,imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine,pyridazine and pyrimidine and the like. Aryl groups also includepolycyclic fused aromatic groups such as naphthyl, quinolyl, indolyl andthe like. The aromatic ring can be substituted at one or more ringpositions with such substituents, e.g., as described above for alkylgroups. Suitable aryl groups include unsubstituted and substitutedphenyl groups. The term “aryloxy” as used herein means an aryl group, asdefined above, having an oxygen atom attached thereto. The term“aralkoxy” as used herein means an aralkyl group, as defined above,having an oxygen atom attached thereto. Suitable aralkoxy groups have 1to 3 separate or fused rings and from 6 to about 18 carbon ring atoms,e.g., O-benzyl.

The term “ceramic precursor”” is intended include any compound thatresults in the formation of a ceramic material.

The term “chiral moiety” is intended to include any functionality thatallows for chiral or stereoselective syntheses. Chiral moieties include,but are not limited to, substituent groups having at least one chiralcenter, natural and unnatural amino-acids, peptides and proteins,derivatized cellulose, macrocyclic antibiotics, cyclodextrins, crownethers, and metal complexes.

The language “chromatographically-enhancing pore geometry” includes thegeometry of the pore configuration of the presently-disclosed materials,which has been found to enhance the chromatographic separation abilityof the material, e.g., as distinguished from other chromatographic mediain the art. For example, a geometry can be formed, selected orconstructed, and various properties and/or factors can be used todetermine whether the chromatographic separations ability of thematerial has been “enhanced”, e.g., as compared to a geometry known orconventionally used in the art. Examples of these factors include highseparation efficiency, longer column life and high mass transferproperties (as evidenced by, e.g., reduced band spreading and good peakshape.) These properties can be measured or observed usingart-recognized techniques. For example, thechromatographically-enhancing pore geometry of the present porousmaterials is distinguished from the prior art particles by the absenceof “ink bottle” or “shell shaped” pore geometry or morphology, both ofwhich are undesirable because they, e.g., reduce mass transfer rates,leading to lower efficiencies.

Chromatographically-enhancing pore geometry is found in porous materialscontaining only a small population of micropores. Porous materials withsuch a low micropore surface area (MSA) give chromatographicenhancements including high separation efficiency and good mass transferproperties (as evidenced by, e.g., reduced band spreading and good peakshape). Micropore surface area (MSA) is defined as the surface area inpores with diameters less than or equal to 34 Å, determined bymultipoint nitrogen sorption analysis from the adsorption leg of theisotherm using the BJH method. As used herein, the acronyms “MSA” and“MPA” are used interchangeably to denote “micropore surface area”.

The term “functionalizing group” includes organic functional groupswhich impart a certain chromatographic functionality to achromatographic stationary phase.

The term “heterocyclic group” includes closed ring structures in whichone or more of the atoms in the ring is an element other than carbon,for example, nitrogen, sulfur, or oxygen. Heterocyclic groups can besaturated or unsaturated and heterocyclic groups such as pyrrole andfuran can have aromatic character. They include fused ring structuressuch as quinoline and isoquinoline. Other examples of heterocyclicgroups include pyridine and purine. Heterocyclic groups can also besubstituted at one or more constituent atoms with, for example, ahalogen, a lower alkyl, a lower alkenyl, a lower alkoxy, a loweralkylthio, a lower alkylamino, a lower alkylcarboxyl, a nitro, ahydroxyl, —CF3, —CN, or the like. Suitable heteroaromatic andheteroalicyclic groups generally will have 1 to 3 separate or fusedrings with 3 to about 8 members per ring and one or more N, O or Satoms, e.g. coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl,furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl,benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl,piperidinyl, morpholino and pyrrolidinyl.

The term “metal oxide precursor” is intended include any compound thatcontains a metal and results in the formation of a metal oxide, e.g.,alumina, silica, titanium oxide, zirconium oxide, or cerium oxide.

The term “monolith” is intended to include a collection of individualparticles packed into a bed formation, in which the shape and morphologyof the individual particles are maintained. The particles areadvantageously packed using a material that binds the particlestogether. Any number of binding materials that are well known in the artcan be used such as, for example, linear or cross-linked polymers ofdivinylbenzene, methacrylate, urethanes, alkenes, alkynes, amines,amides, isocyanates, or epoxy groups, as well as condensation reactionsof organoalkoxysilanes, tetraalkoxysilanes, polyorganoalkoxysiloxanes,polyethoxysiloxanes, and ceramic precursors. In certain embodiments, theterm “monolith” also includes hybrid monoliths made by other methods,such as hybrid monoliths detailed in U.S. Pat. No. 7,250,214; hybridmonoliths prepared from the condensation of one or more monomers thatcontain 0-99 mole percent silica (e.g., SiO₂); hybrid monoliths preparedfrom coalesced porous inorganic/organic particles; hybrid monoliths thathave a chromatographically-enhancing pore geometry; hybrid monolithsthat do not have a chromatographically-enhancing pore geometry; hybridmonoliths that have ordered pore structure; hybrid monoliths that havenon-periodic pore structure; hybrid monoliths that have non-crystallineor amorphous molecular ordering; hybrid monoliths that have crystallinedomains or regions; hybrid monoliths with a variety of differentmacropore and mesopore properties; and hybrid monoliths in a variety ofdifferent aspect ratios. In certain embodiments, the term “monolith”also includes inorganic monoliths, such as those described in G.Guiochon/J. Chromatogr. A 1168 (2007) 101-168.

The term “nanoparticle” is a microscopic particle/grain or microscopicmember of a powder/nanopowder with at least one dimension less thanabout 100 nm, e.g., a diameter or particle thickness of less than about100 nm (0.1 mm), which may be crystalline or noncrystalline.Nanoparticles have properties different from, and often superior tothose of conventional bulk materials including, for example, greaterstrength, hardness, ductility, sinterability, and greater reactivityamong others. Considerable scientific study continues to be devoted todetermining the properties of nanomaterials, small amounts of which havebeen synthesized (mainly as nano-size powders) by a number of processesincluding colloidal precipitation, mechanical grinding, and gas-phasenucleation and growth. Extensive reviews have documented recentdevelopments in nano-phase materials, and are incorporated herein byreference thereto: Gleiter, H. (1989) “Nano-crystalline materials,”Prog. Mater. Sci. 33:223-315 and Siegel, R. W. (1993) “Synthesis andproperties of nano-phase materials,” Mater. Sci. Eng. A168:189-197. Incertain embodiments, the nanoparticles comprise oxides or nitrides ofthe following: silicon carbide, aluminum, diamond, cerium, carbon black,carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, and mixtures thereof. In certain embodiments, the nanoparticlesof the present invention are selected from diamonds, zirconium oxide(amorphous, monoclinic, tetragonal and cubic forms), titanium oxide(amorphous, anatase, brookite and rutile forms), aluminum (amorphous,alpha, and gamma forms), and boronitride (cubic form). In particularembodiments, the nanoparticles of the present invention are selectedfrom nanodiamonds, silicon carbide, titanium dioxide (anatase form),cubic-boronitride, and any combination thereof. Moreover, in particularembodiments, the nanoparticles may be crystalline or amorphous. Inparticular embodiments, the nanoparticles are less than or equal to 100nm in diameter, e.g., less than or equal to 50 nm in diameter, e.g.,less than or equal to 20 nm in diameter.

Moreover, it should be understood that the nanoparticles that arecharacterized as dispersed within the composites of the invention areintended to describe exogenously added nanoparticles. This is incontrast to nanoparticles, or formations containing significantsimilarity with putative nanoparticles, that are capable of formation insitu, wherein, for example, macromolecular structures, such asparticles, may comprise an aggregation of these endogenously created.

The term “substantially disordered” refers to a lack of pore orderingbased on x-ray powder diffraction analysis. Specifically, “substantiallydisordered” is defined by the lack of a peak at a diffraction angle thatcorresponds to a d value (or d-spacing) of at least 1 nm in an x-raydiffraction pattern.

“Surface modifiers” include (typically) organic functional groups whichimpart a certain chromatographic functionality to a chromatographicstationary phase. The porous inorganic/organic hybrid particles possessboth organic groups and silanol groups which may additionally besubstituted or derivatized with a surface modifier.

The language “surface modified” is used herein to describe the compositematerial of the present invention that possess both organic groups andsilanol groups which may additionally be substituted or derivatized witha surface modifier. “Surface modifiers” include (typically) organicfunctional groups which impart a certain chromatographic functionalityto a chromatographic stationary phase. Surface modifiers such asdisclosed herein are attached to the base material, e.g., viaderivatization or coating and later crosslinking, imparting the chemicalcharacter of the surface modifier to the base material. In oneembodiment, the organic groups of a hybrid material, e.g., particle,react to form an organic covalent bond with a surface modifier. Themodifiers can form an organic covalent bond to the material's organicgroup via a number of mechanisms well known in organic and polymerchemistry including but not limited to nucleophilic, electrophilic,cycloaddition, free-radical, carbene, nitrene, and carbocationreactions. Organic covalent bonds are defined to involve the formationof a covalent bond between the common elements of organic chemistryincluding but not limited to hydrogen, boron, carbon, nitrogen, oxygen,silicon, phosphorus, sulfur, and the halogens. In addition,carbon-silicon and carbon-oxygen-silicon bonds are defined as organiccovalent bonds, whereas silicon-oxygen-silicon bonds that are notdefined as organic covalent bonds. A variety of synthetictransformations are well known in the literature, see, e.g., March, J.Advanced Organic Chemistry, 3rd Edition, Wiley, New York, 1985.

The term “nanoparticle” is a microscopic particle/grain or microscopicmember of a powder/nanopowder with at least one dimension less thanabout 100 nm, e.g., a diameter or particle thickness of less than about100 nm (0.1 μm), which may be crystalline or noncrystalline.Nanoparticles have properties different from, and often superior tothose of conventional bulk materials including, for example, greaterstrength, hardness, ductility, sinterability, and greater reactivityamong others. Considerable scientific study continues to be devoted todetermining the properties of nanomaterials, small amounts of which havebeen synthesized (mainly as nano-size powders) by a number of processesincluding colloidal precipitation, mechanical grinding, and gas-phasenucleation and growth. Extensive reviews have documented recentdevelopments in nano-phase materials, and are incorporated herein byreference thereto: Gleiter, H. (1989) “Nano-crystalline materials,”Prog. Mater. Sci. 33:223-315 and Siegel, R. W. (1993) “Synthesis andproperties of nano-phase materials,” Mater. Sci. Eng. A168:189-197. Incertain embodiments, the nanoparticles comprise oxides or nitrides ofthe following: silicon carbide, aluminum, diamond, cerium, carbon black,carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, and mixtures thereof. In certain embodiments, the nanoparticlesof the present invention are selected from diamonds, zirconium oxide(amorphous, monoclinic, tetragonal and cubic forms), titanium oxide(amorphous, anatase, brookite and rutile forms), aluminum (amorphous,alpha, and gamma forms), and boronitride (cubic form). In particularembodiments, the nanoparticles of the present invention are selectedfrom nanodiamonds, silicon carbide, titanium dioxide (anatase form),cubic-boronitride, and any combination thereof. Moreover, in particularembodiments, the nanoparticles may be crystalline or amorphous. Inparticular embodiments, the nanoparticles are less than or equal to 100μm in diameter, e.g., less than or equal to 50 μm in diameter, e.g.,less than or equal to 20 μm in diameter.

Moreover, it should be understood that the nanoparticles that arecharacterized as dispersed within the composites of the invention areintended to describe exogenously added nanoparticles. This is incontrast to nanoparticles, or formations containing significantsimilarity with putative nanoparticles, that are capable of formation insitu, wherein, for example, macromolecular structures, such asparticles, may comprise an aggregation of these endogenously created.

Nanoparticles are of great scientific interest as they are effectively abridge between bulk materials and atomic or molecular structures. A bulkmaterial should have constant physical properties regardless of itssize, but at the nano-scale this is often not the case. Size-dependentproperties are observed such as quantum confinement in semiconductorparticles, surface plasmon resonance in some metal particles andsuperparamagnetism in magnetic materials.

The properties of materials change as their size approaches thenanoscale and as the percentage of atoms at the surface of a materialbecomes significant. For bulk materials larger than one micrometer thepercentage of atoms at the surface is minuscule relative to the totalnumber of atoms of the material. The interesting and sometimesunexpected properties of nanoparticles are partly due to the aspects ofthe surface of the material dominating the properties in lieu of thebulk properties. In certain embodiments, selection of the nanoparticleaffects the selectivity of the chromatographic material. For example,dispersion of TiO₂ or zirconium oxide could modify the surface charge,surface acidity, and therefore, the chromatographic selectivity.

The language, “composite material” and the term “composite” are usedinterchangeably herein to describe the engineered materials of theinvention composed of one or more components described herein incombination with dispersed nanoparticles, wherein eachcomponent/nanoparticle remains separate and distinct on a macroscopiclevel within the finished structure. The composite material of thepresent invention is independent of form, and may be monolithic orparticulate in nature. Moreover, a short-hand convention may be used todescribe a composite material containing a dispersed nanoparticle,Np/(A)_(w)(B)_(x)(C)_(y), and may be understood as follows: the symbolicrepresentation to the left of the slash mark represents the dispersednanoparticle, and the symbolic representations to the right of the slashmark represent the components that comprise the material that thenanoparticle (noted on the left of the slash mark) is dispersed within.In certain embodiments, the composite materials of the present inventionmay be nanocomposites, which are known to include, at least, forexample, nano/nano-type, intra-type, inter-type, and intra/inter-type.(Nanocomposites Science and Technology, edited by P. M. Ajayan, L. S.Schadler, P. V. Braun, Wiley-VCH (Weinheim, Germany), 2003) The terms“material having a high thermal conductivity”, “high thermalconductivity core”, and a “high thermal conductivity additive” aredefined as a material, core material, or composite additive having athermal conductivity greater than 20 W/(m·K). In various embodiments theadditive has a thermal conductivity ranges from: about 20 W/(m·K) to notmore than 3500 W/(m·K); about 100 W/(m·K) to not more than 3300 W/(m·K);and 400 W/(m·K) to not more than 3000 W/(m·K). High thermal conductivitycores or additives can be, for example and without limitation, a 0.1-8μm core particle, nanoparticle additives, or a metal oxide precursor. Invarious embodiments the high thermal conductivity core or additiveincludes (but is not limited to) aluminum, copper, gold, and diamonds.

A “high thermal diffusivity” core or additive is defined as an additiveused in a superficially porous materials as having a thermal diffusivitygreater than 20 mm²/s. In various embodiments the core or additive has athermal diffusivity ranges from: about 20 mm²/s to not more than 2000mm²/s; about 100 mm²/s to not more than 1600 mm²/s; and 150 mm²/s to notmore than 1400 mm²/s. This high thermal conductivity core or additivecan be a 0.1-8 μm core particle, nanoparticle additives, or a metaloxide precursor. In various embodiments the high thermal conductivitycore or additive includes (but is not limited to) aluminum, copper,gold, and diamonds.

A “high thermal conductivity superficially porous material (orparticle)” is defined as a material that has improved thermalconductivity or improved thermal diffusivity over a porous silicaparticle of the same size. In various embodiments the higher thermalconductivity superficially porous material is a material that hasimproved thermal conductivity or thermal diffusivity over asuperficially porous silica particle of the same size. In variousembodiments the higher thermal conductivity superficially porousmaterial is a material that has improved thermal conductivity over afully porous hybrid particle of the same size. Determination of particlethermal conductivity can be made by the method of Gritti and Guiochon[J. Chromatogr. A, 2010, 1217, 5137) taking into account differences inbulk material properties, pore volume, surface modification type andcoverage.

The terms “magnetic material”, “magnetic cores” and “magnetic additives”are defined as a material, core material, or composite additive that gasa mass magnetization (o, magnetic moment per unit mass, magneticsaturation or saturation magnetization) at room temperature greater than15 emu/g (A m²/kg). This includes ferromagnetic and ferrimagneticmaterials, including (but is not limited to): magnetite (ferrous ferricoxide); maghemite; yttrium iron garnet, cobalt, CrO₂; and ferritescontaining iron and Al, Mg, Ni, Zn, Mn or Co). Magnetic core particlesdo not include other oxides of iron, including hematite and goethite,that have mass magnetization values less than 10 emu/g. Hematite (0.4emu/g) is considered antiferromagnetic at room temperature.

As used herein, the term “fines” refers to undesired materials generatedin the processes of the invention that are below the 10 vo % of thetarget particle size distribution. Fines can be formed from reseedingevents or from particle breakage. Resulting fines can be nonporous orfully porous. Often fines are substantially smaller than the 10 vol % ofthe target particle size distribution. Often fines are <1 um in size.Very small fines can cause problems in chromatography in that thepercolate through the packed bed and get stuck in the outlet frit. Thisgenerates increased column pressure. Alternatively fines small enough topercolate through the packed bed and outlet frit can result in problemswith detectors and can contaminate a product. Problems with detectorinclude clogging flow channels, blocking detector windows, and anomalousdetector readings. Such issues can reduce the lifetime of a detector andcan require extensive cleaning protocols. Such issues can also impactthe precision, accuracy, reliability, reproducibility, and robustness ofanalytical data generated. Fines can be removed by classification.

As used herein, the terms “aggregates” and “agglomerates” refer toundesired materials generated in the processes of the invention that arelarger than the 90 vol % of the target particle size distribution.aggregates and/or agglomerates can form from imperfections of the corematerial, improper mixing or dispersion in the process, or excessiveforces during workup. Aggregates and agglomerates can impact theefficiency, permeability, reproducibility and robustness of packed bedswithin chromatographic columns. It is difficult to optimally pack achromatographic column with materials having an elevated amount ofaggregates and agglomerates. Aggregates and agglomerates can break apartwithin a packed bed structure when exposed to high pressures and shears.This can result in a mechanical instability of the packed bed and theresult of a void on the top of the column. This breaking of aggregatesand agglomerates can also result in the generation of fines. Aggregatesand agglomerates can be removed by classification.

Hybrid Inorganic/Organic Superficially Porous Particles.

Hybrid particle technologies are highly desirable for manychromatographic applications due to the increased chemical stability andreduced silanol activity they provide. One key advantage of hybridparticles over silica and hybrid coated silica particles inchromatographic applications is their superior column stability whenused with alkaline mobile phases (pH 8-12). Silica and hybrid coatedsilica packing materials have limited lifetimes under these conditionsdue to the dissolution of the silica and collapse of the packed bed.

Currently there are no means to prepare hybrid superficially porousparticle for chromatographic applications. This is due in part to theneed to utilize one or more calcination steps (≥500° C.) during thesuperficially porous particle synthesis. Such temperatures degrade mostorganic groups of a hybrid material.

Approach to the Synthesis of Hybrid Superficially Porous Particles.

In one approach spherical silica or hybrid non-porous cores are preparedfollowing standard protocols. A superficially porous layer is formedusing two or more of the following; TEOS, a thermally degradableorganofunctional silane (e.g., acetoxypropyltrialkoxysilane orbromoethyltrialkoxysilane) along with a more thermally stable hybridsilanes, such as (but not limited to) phenylene bridged silanes. In thisprocess lower temperature thermal treatment (<500° C.) is performed todegrade the thermally degradable organofunctional silane as a means tointroduce porosity, while maintaining the more thermally stable hybridgroup. The temperature is determined by TGA experiments performed inair. Additional steps of classification, pore modification, acidtreatment and bonding are performed, as detailed herein.

In another approach, spherical hybrid non-porous cores are preparedfollowing standard protocols. A superficially porous layer is preparedusing a surfactant or a mixed surfactant approach using one or moresilanes that include (but is not limited to) TEOS, a lower temperaturedegradable organofunctional silane (e.g., acetoxypropyltrialkoxysilaneor bromoethyltrialkoxysilane), ethylene bridged alkoxysilanes, orphenylene bridged alkoxysilanes. The surfactant is removed using an acidethanol process (e.g., hydrochloric acid in ethanol). Alternatively, thesurfactant is removed by thermal treatment (<500° C.) at a temperaturethat preserves the hybrid group, while removing the surfactant. Thistemperature is determined by TGA experiments performed in air.Alternatively the surfactant is removed by oxidation (e.g., ozonolysis).Alternatively, one or more of the surfactants used in this process areselected from the group of acid labile, base labile, or other labilesurfactants. These labile surfactants can be reacted and removed laterby selecting the correct chemical conditions (e.g., acid hydrolysis,base hydrolysis, reduction or oxidation, hydrogenation orhydrogenolysis). Additional steps of classification, pore modification,acid treatment and bonding are performed, as detailed above. In anotherapproach, spherical silica or hybrid non-porous cores are preparedfollowing standard protocols. Separately a hybrid sol (<100 nm) solutionis prepared using one or more silanes that include (but is not limitedto) TEOS, lower temperature degradable organofunctional silane (e.g.,acetoxypropyltrialkoxysilane or bromoethyltrialkoxysilane), ethylenebridged alkoxysilanes, or phenylene bridged alkoxysilanes. A uniformsuperficially porous layer is then prepared in a layer-by-layer approachusing a suitable positively charged polyelectrolyte. Suitablepolyelectrolytes include (but is not limited to) linear, branched, andblock polymers containing one or more of the following groups; alkyl,cycloalkyl, aryl, ethylene oxide groups along with one or more of thefollowing groups; primary, secondary, tertiary and quaternary aminogroups, pyrrolidone, pyridine, and imidazole. The polyelectrolyte isremoved by thermal treatment (<500° C.) at a temperature that preservesthe hybrid group, while removing the polyelectrolyte. This temperatureis determined by TGA experiments performed in air. Alternatively thepolyelectrolyte is removed by ozonolysis. Additional steps ofclassification, pore modification, acid treatment and bonding areperformed, as detailed herein.

Higher Thermal Conductivity Superficially Porous Particles.

Recent studies (Gritti, F. Journal of Chromatography A, 1217 (2010)5069-5083) suggest superficially porous silica particles havesignificantly higher thermal conductivities when compared to fullyporous particles of the same size. This higher thermal conductivity isone reason why superficially porous particles were noted to haveimproved chromatographic performance.

Approach to the Synthesis of Higher Thermal Conductivity SuperficiallyPorous Particles

It is well known that many materials have higher thermal conductivitiesthan silica. Included in this is diamond. Micron and sub-micron sizeddiamond particles are well known, and can be prepared from natural andchemical processes. Alternatively diamond nanoparticles can beincorporated within non-porous cores (including non-porous silica) Theuse of a diamond core (0.5-3 μm) for a superficially porous particle mayresult in a measurable increase in thermal conductivity when compared toa silica based superficially porous particle of comparable size. Inorder to reduce undesired chromatographic interactions that may resultfrom a diamond core, a non-porous silica or hybrid surface coating maybe advantageously used. This surface coating step may be advantageouslyrepeated or performed in a growth-process to achieve the desiredthickness. Calcination and surface rehydroxylation may be advantageouslyused at the end of this step.

The superficially porous layer may be silica or hybrid, and can beprepared in any of the processes described herein. Additional steps ofclassification, calcination, pore modification, re-calcination,rehydroxylation and bonding are then performed (as required), asdetailed herein.

Improved Permeability Using Superficially Porous Technologies.

The impact of particle attributes on packed bed permeability can bemodeled using the Kozeny-Carman equation. One can use this equation tomodel pressures required to push a solvent through a column packed withparticles that varies in interstitial fraction (e) and particle size(dr). Pressure changes with the square of particle size (based on numbercount), while column efficiency correlates linearly with particle size(based on volume count). As a result, decreasing particle size toimprove efficiency results in a dramatic increase in column pressure.While chromatographic systems exist that can handle increased columnpressures, it is desirable to obtain the lowest column pressuresavailable for a given particle size. One means to achieve this is todecrease the difference between the number and volume average particlesize. For example, using particles that are monodisperse. Monodispersenon-porous, fully porous and superficially porous particles have beenreported. For the latter the ability to prepare monodisperse particlesis a function of the non-porous core as well as the uniformity of theporous layer. As described herein, the materials of the instantinvention provide improved permeability as well as improved chemicalstability with high pH mobile phases.

Approach to the Synthesis of Superficially Porous Particles that FormPacked Beds with Improved Permeability.

A further improvement in permeability can be achieved if the particleshape is modified. For example, a uniform micron-sized doughnut, rod,dumbbell, star, or bent-rod-shaped cores is used in place of a highlyspherical core. Additional shapes include (but not limited to) spirals,discoidal, concave disks, spools, rings, helix, saddles, cross, cube,derby, helix, cylinders, and tubes. Examples of dumbbell, doughnut, rod,spiral, and gyroid particles have been reported {Doshi, N. PNAS, 2009,106, 51, 21495; Alexander, L. Chem. Commun., 2008, 3507; Naik, S. J.Phys. Chem. C 2007, 111, 11168; Pang, X. Microporous and MesoporousMaterials 85 (2005) 1; Kievsky, Y. IEEE Transactions on Nanotechnology,2005, 4, 5, 490; Sugimoto, T. in Monodispersed Particles, (ElsevierScience BV, Amsterdam) 2001; Ozin, G. Adv. Mater., 1997, 9, 662}.

Important factors for the non-spherical cores is that they be relativelyuniform in dimensions, free-flowing, non-porous, and mechanically strongenough for use in HPLC and UPLC. The composition of these cores may beselected from (but is not limited to) silica, metal oxides, diamonds,heavily cross linked polymers, and hybrid materials. Improvements incore uniformity can be achieved through classification. A reduction inporosity can be achieved by pore filling with a similar or differentcomposition (e.g., pore filling a silica material with a crosslinkedpolymer composition). Improvements in mechanical strength is achieved byincreasing crosslinking with the same or different composition (e.g.,creating a silica network within a polymer composition), or bycalcination. For the latter, higher temperatures (e.g., >800° C.) may beadvantageously used.

In order to reduce undesired chromatographic interactions due to thecore, a non-porous surface coating with a silica, hybrid, or polymericcomposition may be advantageously used. This surface coating step mayneed to be repeated or performed in a growth-process to achieve thedesired thickness. To ensure that the core morphology is notsubstantially modified, this step advantageously provides a uniformsurface layer. Calcination and surface rehydroxylation may beadvantageously used at the end of this step.

A uniform silica or hybrid superficially porous layer may be formed fromany one of the processes described above. To ensure the core morphologyis not substantially modified, this step advantageously yields a highlyuniform porous layer. Additional steps of classification, calcination,pore modification, re-calcination, rehydroxylation and bonding are thenperformed (as required) as detailed above. These non-sphericalsuperficially porous materials can be packed in chromatographic columnsindividually or as mixtures with other shapes, or with sphericalparticles. It is important to optimize column packing conditions forthese mixed systems. Considerations of maintaining similar dispersion,bulk density and settling rates between the different materials need tobe made.

Improved Process to Prepare Zuperficially Porous Materials.

As noted herein, the AMT process and the University of Cork process bothrequire repeated in-process workups using centrifugation followed byredispersion during the formation of the superficially porous layer. Theconcerns with repeated centrifugation is aggregation/agglomeration,difficulty redispersing particles, product uniformity, and long labortimes required for this process. Aggregation and agglomeration areextremely detrimental for this process. It is possible foraggregates/agglomerates to be further coated in both of these processes.By its nature repeated centrifugation allows for these un-aged, ‘green’materials to get close to each other. Excessive centrifugation time andg-forces can results in a tight bed structure that can be hard toredisperse. Filtration (including tangential filtration) is analternative to centrifugation that allows for a less compact bed to beformed. Unfortunately the time period required to filter <3 μm materialsthat may be laden with sub-micron fines is prohibitive. These sub-micronfines can readily clog the filter material preventing completefiltration to occur.

There are also many methods available to redisperse particles, includingsonication using sonic baths, in-line sonicators, in-tank sonicators,sonic horns, rotor-stator mixers, milling, low shear and high shearmixing (e.g., saw-tooth impellers). Optimization of amplitude, frequencyand pulse sequences is used for optimal sonication. Adjusting theconductivity, pH and surfactant mixture can also be used to optimallyredisperse particles (through solvent washes, or controlled order ofaddition of reagents). One concern for these redispersion methods is thepotential to harm the superficially porous layer. It is expected thatelevated shears may result in a fracturing of the porous layer. Theresulting material may have bare-spots, or non-uniform porous layers.

A further concerns is the long reaction times required for an iterativeprocess, such as those described by AMT and the University of Cork.While such materials can be prepared on a laboratory and batch scale,the times required for these processes can exceed those typically usedfor the synthesis of fully porous particles.

Another concern for uniform shell processes such is the impact ofreseeding. Reseeded particles (<0.5 μm) can emerge during the growthstep. If they are not effectively removed, the will start to growpreferentially over the larger porous layer, solid core materials. Atsome point the two particle distributions can overlap. The end result ofthis, after further processing steps, is the overlapping mixture ofsuperficially porous and fully porous particles. These overlappingmixture of particles are difficult to separate, quantify or understandthe impact on chromatographic performance (including chromatographicreproducibility).

Approach to the Improved Synthesis of Superficially Porous Materials.

In this approach magnetic capture methods are used to collect magneticcore particles in place of centrifugation or filtration. These methodsinclude in-tank, in-line, or off-line magnetic capture.

In-tank magnetic capture uses a removable magnetic rod (or alternativelyan electromagnet) placed within a removable or permanent glass sleeve orbaffle. In this approach the magnetic rod is placed within the glasssleeve during the time of capture. After the remaining reaction solutionis emptied and a new wash or reaction solvent is added, the magnetic rodis removed and bound magnetic core particles are redispersed.Alternatively, an external magnet is placed on the side of the reactorallowing magnetic core particles to be captured on the reactorside-wall. After the remaining reaction solution is emptied and a newwash or reaction solvent is added, the external magnet is removed andbound magnetic core particles are redispersed.

The in-line magnetic capture method involves pumping the reactionsolution in a recirculation loop through a collection container. Thiscollection container is placed within a magnetic holding block. Magneticcore particles are collected in this container. After the remainingreaction solution is emptied and a new wash or reaction solvent isadded, the collection container is removed from the magnetic holdingblock and the bound magnetic core particles are redispersed as they arepumped back into the reaction vessel. By using the appropriate sizedcollection container (advantageously containing one or more flatsurfaces) this approach has an advantage in that it allows for goodcontrol of the surface area exposed to the magnetic field.

The off-line magnetic capture method is similar to filtration in thatthe reaction solution is transferred to a secondary vessel. In thissecondary vessel, a magnetic field is applied to allow for thecontrolled collection of magnetic core particles. Reaction solution orwash solvents are removed by filtration, decanting, or by siphon.Magnetic core particles are redispersed in the appropriate solvent andtransferred back to the reaction vessel.

During the magnetic capture step for all of these approaches, a loosecollection of magnetic core particles is formed. These collections ofcore particles are less dense than the cake formed by excessivecentrifugation. As a result these particles are easier to redisperse.The manner of redispersing magnetic core particles is similar to theapproaches described above.

In this approach a non-porous magnetic core is used in place of anon-porous silica or hybrid core. This magnetic core can contain (but isnot limited to) magnetic forms of iron oxides, iron, metals, metaloxides, chromium dioxide, ferrites, or cobalt. Advantageously themagnetic core contains magnetite, maghemite. The magnetic core can existas a pure metal or metal oxide or exist in combination with a secondmaterial that includes (but is not limited to) silica, hybrid, polymer,or non-magnetic materials. For example, a magnetic core can be formed byincorporating <100 nm magnetite or cobalt nanoparticles withinnon-porous silica or polymer particles. The magnetic nanoparticles canbe homogeneously dispersed nanoparticles or dispersed clusters ofnanoparticles within this material, adsorbed only to the surface, orcontained only in the interior of the non-porous core particles.Alternatively 0.3-1.5 μm magnetite or cobalt particles can be used asthe non-porous core. Magnetic capture methods are used in this processin place of centrifugation or filtration.

In order to reduce undesired chromatographic interactions due to thecore, a non-porous surface coating with a silica, hybrid, or polymericcomposition may be advantageously used. This surface coating step may berepeated or performed in a growth-process to achieve the desiredthickness. Magnetic capture methods are used in this process in place ofcentrifugation or filtration. To ensure that the core morphology is notsubstantially modified, this step advantageously provides a uniformsurface layer. Calcination and surface rehydroxylation may beadvantageously used at the end of this step.

A uniform silica or hybrid superficially porous layer may be formed fromany one of the processes described above. To ensure the core morphologyis not substantially modified, this step advantageously yields a highlyuniform porous layer. Magnetic capture methods are used in this processin place of centrifugation or filtration. Additional steps ofclassification, calcination, pore modification, re-calcination,rehydroxylation and bonding are then performed (as needed) as detailedabove.

Considering the problem associated with reseeded particles for uniformlayer processes such as the novel one described above or the Universityof Cork process, a magnetic core particle allows for a unique means toseparate the porous layer materials from reseeded particles. This can beutilized in-process or during product workup.

The use of magnetic core particles as well as magnetic capture methodsallows for a unique process of automating the synthesis of superficiallyporous particles. The use of in-tank magnetic capture (e.g., usingelectromagnets) allows for full automation of particle collection.Automated bottom valves and solvent addition valves, are used to fullyautomate synthesis conditions. In-tank or in-line particle sizemeasurements are used to monitor reaction performance and determinedreaction completion.

Core and Shell Materials.

The invention provides superficially porous materials, particles and/ormonoliths comprising a substantially nonporous inorganic/organic hybridcore and one or more layers of a porous shell material surrounding thecore.

In certain embodiments, the superficially porous material of theinvention a substantially narrow particle size distribution. In certainother embodiments, the 90/10 ratio of particle sizes is from 1.00-1.55.In specific embodiments, the 90/10 ratio of particle sizes is from1.00-1.10 or from 1.05-1.10. In other specific embodiments, the 90/10ratio of particle sizes is from 1.10-1.55; from 1.10-1.50; or from1.30-1.45.

In certain embodiments, the superficially porous material of theinvention, wherein the material has chromatographically enchancing poregeometry. That is, in some embodiments, the superficially porousmaterial of the invention has only a small population of micropores.

Hybrid Core

The novel inorganic/organic hybrid materials of the invention comprise asubstantially nonporous inorganic/organic hybrid core. That is, theinorganic/organic hybrid core of the invention has a pore volume of lessthan 0.10 cc/g. The hybrid core may possess or not possess a copolymericstructure. In certain embodiments, the hybrid core may or may not posessnanoparticles of a composite material.

Thus, in one aspect, the invention comprises an inorganic/organic hybridcore, wherein the inorganic portion of the hybrid core is present in anamount ranging from about 0 molar % to not more than about 99 molar %,wherein the pores of the core are substantially disordered. In otherembodiments, the inorganic portion of the hybrid core is present in anamount from about 0 molar % to not more than about 75 molar %. In stillother embodiments, the inorganic portion of the hybrid core is presentin an amount from about 0 molar % to not more than about 50 molar %. Inyet other embodiments, the inorganic portion of the hybrid core ispresent in an amount from about 0 molar % to not more than about 25molar %.

In various embodiments of the aforementioned aspect of the invention,the amount of the inorganic portion of the hybrid core ranges from:about 0 molar % to not more than about 1 molar %; about 0 molar % to notmore than about 2 molar %; about 0 molar % to not more than about 3molar %; about 0 molar % to not more than about 4 molar %; about 0 molar% to not more than about 5 molar %; about 0 molar % to not more thanabout 6 molar %; about 0 molar % to not more than about 7 molar %; about0 molar % to not more than about 8 molar %; about 0 molar % to not morethan about 9 molar %; about 0 molar % to not more than about 10 molar %;about 0 molar % to not more than about 11 molar %; about 0 molar % tonot more than about 12 molar %; about 0 molar % to not more than about13 molar %; about 0 molar % to not more than about 14 molar %; about 0molar % to not more than about 15 molar %; about 0 molar % to not morethan about 16 molar %; about 0 molar % to not more than about 17 molar%; about 0 molar % to not more than about 18 molar %; about 0 molar % tonot more than about 19 molar %; about 0 molar % to not more than about20 molar %; about 0 molar % to not more than about 21 molar %; about 0molar % to not more than about 22 molar %; about 0 molar % to not morethan about 23 molar %; about 0 molar % to not more than about 24 molar%; and about 0 molar % to not more than about 25 molar; about 0 molar %to not more than about 26 molar %; about 0 molar % to not more thanabout 27 molar %; about 0 molar % to not more than about 28 molar %;about 0 molar % to not more than about 29 molar %; about 0 molar % tonot more than about 30 molar %; about 0 molar % to not more than about31 molar %; about 0 molar % to not more than about 32 molar %; about 0molar % to not more than about 33 molar %; about 0 molar % to not morethan about 34 molar %; about 0 molar % to not more than about 35 molar%; about 0 molar % to not more than about 36 molar %; about 0 molar % tonot more than about 37 molar %; about 0 molar % to not more than about38 molar %; about 0 molar % to not more than about 39 molar %; about 0molar % to not more than about 40 molar %; about 0 molar % to not morethan about 41 molar %; about 0 molar % to not more than about 42 molar%; about 0 molar % to not more than about 43 molar %; about 0 molar % tonot more than about 44 molar %; about 0 molar % to not more than about45 molar %; about 0 molar % to not more than about 46 molar %; about 0molar % to not more than about 47 molar %; about 0 molar % to not morethan about 48 molar %; about 0 molar % to not more than about 49 molar%; about 0 molar % to not more than about 50 molar %; about 0 molar % tonot more than about 100 molar %; about 50 molar % to not more than about99 molar %; and about 75 molar % to not more than about 99 molar %.

The inorganic portion of the hybrid core may be alumina, silica (SiO₂),titanium oxide, zirconium oxide, or ceramic materials. The hybridmaterial of the invention in which the inorganic portion is SiO₂ isparticularly advantageous.

In one embodiment, the organic content is from about 1 to about 40%carbon. In another embodiment, the organic content is from about 5 toabout 35% carbon. In yet another embodiment, the invention provides aporous inorganic/organic hybrid particle, wherein the organic content isfrom about 25 to about 40% carbon. In a further embodiment, the organiccontent is from about 25 to about 35% carbon. In a further embodiment,the organic content is from about 5 to about 15% carbon.

In one embodiment, the hybrid material of the invention comprises ahybrid core of formula I:(SiO₂)_(d)/[R²((R)_(p)(R)_(q)SiO_(t))_(m)]  (I)wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

p and q are each independently 0.0 to 3.0,

t is 0.5, 1.0, or 1.5;

d is 0 to about 30;

m is an integer from 1-20; wherein R, R¹ and R² are optionallysubstituted; provided that: (1) when R² is absent, m=1 and

${t = \frac{\left( {4 - \left( {p + q} \right)} \right)}{2}},$when 0<p+q≤3; and

-   -   (2) when R² is present, m=2-20 and

${t = \frac{\left( {3 - \left( {p + q} \right)} \right)}{2}},$when p+q≤2.

In certain embodiments, R² is absent, t=1.5 when p+q=1; or t=1 whenp+q=2. In other embodiments, R² is present, p=0, q is 0 or 1 and t=1.5when q=0; or t=1 when q=1.

In certain embodiments, R² is absent. In other embodiments, R² ispresent. In embodiments of formula I in which R² is present, theinvention comprises a hybrid core of formula I, wherein p is 0, q is 0,t is 1.5, m is 2, and R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, orC₁-C₁₈ heteroaryl; wherein each R² is attached to two or more siliconatoms. In a further embodiment, d is 0. In another embodiment, d is0.11. In still another embodiment, d is 0.33. In certain embodiments, dis 0.83.

In other embodiments of formula I in which R² is present, the inventioncomprises a hybrid core of formula I, wherein d is 0, q is 0, and R² isC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, or C₁-C₁₈ heteroaryl; and wherein each R²is attached to two or more silicon atoms. In a further embodiment, p is0, 1, or 2. In another further embodiment, t is 1.0 or 1.5. In anotherembodiment, m is 1 or 2.

Certain advantageous embodiments of hybrid cores of formula I in whichR² is present are set forth in the following table (product numbersrefer to the numbers used in the examples set forth below):

Product Reference In reference Formula d p q t m U.S. Pat. No. 6,686,035B2 3i (SiO2)_(0.96)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.04) 27 0 0 1.5 2 U.S.Pat. No. 6,686,035 B2 3j (SiO2)_(0.89)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.11)8 0 0 1.5 2 U.S. Pat. No. 6,686,035 B2 3k(SiO2)_(0.85)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.2) 4 0 0 1.5 2 U.S. Pat. No.6,686,035 B2 3l (SiO2)_(0.66)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.33) 2 0 0 1.52 U.S. Pat. No. 6,686,035 B2 3n(SiO2)_(0.5)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.5) 1 0 0 1.5 2 WO 2008/103423A1 13a (SiO2)_(0.45)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.55) 0.83 0 0 1.5 2 WO2008/103423 A1 13b, 13d-13g(SiO2)_(0.25)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.75) 0.33 0 0 1.5 2 WO2008/103423 A1 13c (SiO2)_(0.1)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(0.9) 0.11 0 01.5 2 WO 2008/103423 A1 5h (O_(1.5)SiCH₂CH₂SiO_(1.5)) 0 0 0 1.5 2 WO2008/103423 A1 11a-i, l-q, t(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(YSiO_(1.5))_(1−x) 0 0, 1 0 1.5, 2, 1 1.5WO 2008/103423 A1 11j(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(YSiO_(1.5))_(w)(ZSiO_(1.5))_(1−x−w) 0 0,1, 1 0, 0, 0 1.5, 2, 1, 1 1.5, 1.5 WO 2008/103423 A1 11k, s(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(O_(1.5)Si—Y—SiO_(1.5))_(1−x−w) 0 0, 0 0,0 1.5, 2, 2 1.5 WO 2008/103423 A1 11e(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(Y₂SiO₁)_(1−x) 0 0, 2 0, 0 1, 5, 2, 1 1.0WO 2008/103423 A1 11r (O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(FSiO_(1.5))_(1−x) 00, 0 0, 0 1.5, 2, 1 1.5

In another embodiment, the hybrid material of the invention comprises ahybrid core of formula II:(SiO₂)_(d)/[(R)_(p)(R¹)_(q)SiO_(t)]  (II)wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

d is 0 to about 30;

p and q are each independently 0.0 to 3.0, provided that when p+q=1 thent=1.5; when p+q=2 then t=1; or when p+q=3 then t=0.5.

In yet another embodiment, the hybrid material of the inventioncomprises a hybrid core of formula III:(SiO₂)_(d)/[R²((R¹)_(r)SiO_(t))_(m)]  (III)wherein,

R¹ is C₁-C₁₈ alkoxy, C₁-C₁ alkyl, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

d is 0 to about 30;

r is 0, 1 or 2, provided that when r=0 then t=1.5; when r=1 then t=1; orwhen r=2, then t=0.5; and

m is an integer from 1-20.

In various embodiments, the invention comprises a hybrid core offormulas I and II, wherein R is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, or C₁-C₁₈alkyl. In various embodiments, the invention comprises a hybrid core offormulas I, II and III, wherein R¹ is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, orC₁-C₁₈ alkyl. In various embodiments, the invention comprises a hybridcore of formulas I and III, wherein R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl,C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl,or C₁-C₁₈ heteroaryl.

In yet another embodiment, the hybrid material of the inventioncomprises a hybrid core of formula IV:(A)_(x)(B)_(y)(C)_(z)  (IV)wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block; A is an organic repeat unit which iscovalently bonded to one or more repeat units A or B via an organicbond; B is an organosiloxane repeat unit which is bonded to one or morerepeat units B or C via an inorganic siloxane bond and which may befurther bonded to one or more repeat units A or B via an organic bond; Cis an inorganic repeat unit which is bonded to one or more repeat unitsB or C via an inorganic bond; x and y are positive numbers, and z is anon negative number, wherein x+y+z=1. In certain embodiments, z=0, then0.002≤x/y≤210, and when z≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In a related embodiment, the hybrid material of the invention maycomprise a hybrid core of formula V:(A)_(x)(B)_(y)(B*)_(y*)(C)_(z)  (V)wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block; A is an organic repeat unit whichis covalently bonded to one or more repeat units A or B via an organicbond; B is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond, B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization; C is aninorganic repeat unit which is bonded to one or more repeat units B orB* or C via an inorganic bond; x and y are positive numbers and z is anon negative number, wherein x+y+z=1. In certain embodiments, when z=0,then 0.002≤x/(y+y*)≤210, and when z≠0, then 0.0003≤(y+y*)/z≤500 and0.002≤x/(y+y*+z)≤210.

Repeat unit A may be derived from a variety of organic monomer reagentspossessing one or more polymerizable moieties, capable of undergoingpolymerization, e.g., a free radical-mediated polymerization. A monomersmay be oligomerized or polymerized by a number of processes andmechanisms including, but not limited to, chain addition and stepcondensation processes, radical, anionic, cationic, ring-opening, grouptransfer, metathesis, and photochemical mechanisms.

A may also be one of the following:

wherein each R is independently H or a C₁-C₁₀ alkyl group (e.g, methyl,ethyl, or propyl); m is an integer of from 1 to about 20; n is aninteger of from 0 to 10; and Q is hydrogen, N(C₁₋₆alkyl)₃,N(C₁₋₆alkyl)₂(C₁₋₆alkyl-SO₃), or C(C₁₋₆hydroxyalkyl)₃.

Repeat unit B may be derived from several mixed organic-inorganicmonomer reagents possessing two or more different polymerizablemoieties, capable of undergoing polymerization, e.g., a freeradical-mediated (organic) and hydrolytic (inorganic) polymerization. Bmonomers may be oligomerized or polymerized by a number of processes andmechanisms including, but not limited to, chain addition and stepcondensation processes, radical, anionic, cationic, ring-opening, grouptransfer, metathesis, and photochemical mechanisms.

B may also be one of the following:

Repeat unit C may be —SiO₂— and may be derived from an alkoxysilane,such as tetraethoxysilane (TEOS) or tetramethoxysilane (TMOS).

In one embodiment, A is a substituted ethylene group, B is aoxysilyl-substituted alkyl group, and C is a oxysilyl group, for examplethe following:

A specific embodiment of a porous hybrid core of formula IV is:

wherein

R₁ is H, F, Cl, Br, I, lower alkyl (e.g., CH₃ or CH₂CH₃);

R₂ and R₃ are each independently H, F, Cl, Br, I, alkane, substitutedalkane, alkene, substituted alkene, aryl, substituted aryl, cyano,ether, substituted ether, embedded polar group;

R₄ and R₅ are each independently H, F, Cl, Br, I, alkane, substitutedalkane, alkene, substituted alkene, aryl, substituted aryl, ether,substituted ether, cyano, amino, substituted amino, diol, nitro,sulfonic acid, cation or anion exchange groups,

0≤a≤2x, 0≤b≤4, and 0≤c≤4, provided that b+c≤4 when a=1;

1≤d≤20,

0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In still another embodiment, the hybrid cores are spherical. In afurther embodiment, the spherical core has a non-crystalline oramorphous molecular ordering. In a further embodiment, the sphericalcore has a non-periodic pore structure.

In another embodiment, the hybrid core has an average size of about 0.1μm to about 300 μm. In a further embodiment, the hybrid core has anaverage size of about 0.1 μm to about 30 μm. In a further embodiment,the hybrid core has an average size of about 0.5 μm to about 30 μm. In afurther embodiment, the hybrid core has an average size of about 0.9 μmto about 10 μm. In a further embodiment, the hybrid core has an averagesize of about 1.0 μm to about 3.0 μm.

In certain embodiments, the hybrid core material of the invention asubstantially narrow particle size distribution. In certain otherembodiments, the 90/10 ratio of particle sizes is from 1.00-1.55. Inspecific embodiments, the 90/10 ratio of particle sizes is from1.00-1.10 or from 1.05-1.10. In other specific embodiments, the 90/10ratio of particle sizes is from 1.10-1.55; from 1.10-1.50; or from1.30-1.45.

In certain embodiments, the hybrid core is hydrolytically stable at a pHof about 1 to about 14. In one embodiment, the hybrid core ishydrolytically stable at a pH of about 10 to about 14. In anotherembodiment, the hybrid core is hydrolytically stable at a pH of about 1to about 5.

In one embodiment, the invention comprises an inorganic/organic hybridcore as described herein, wherein the core is formed by hydrolyticcondensation of one or more monomers selected from the group consistingof:

wherein R, R¹ and R are as defined previously; X is C₁-C₁₈ alkoxy orC₁-C₁₈ alkyl; and n is 1-8.

In a further embodiment, the monomer is 1,2-bis(triethoxysilyl)ethane:

In another further embodiment, the monomer is1,2-bis(methyldiethoxysilyl)ethane:

or 1,8-bis(triethoxysilyl)octane:

In certain embodiments, the momomer is phenyltriethoxysilane;phenyltrimethoxysilane; phenylethyltriethoxysilane;phenylethyltrimethoxysilane; ethyltriethoxysilane;ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilanediethyldiethoxysilane; diethyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(trimethoxysilyl)ethane; 1,2-bis(triethoxysilyl)ethane;1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane;vinyltriethoxysilane; vinyltrimethoxysilane;mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane;1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene;1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane;1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(triethoxysilylethyl)benzene; 1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane; hexyltrimethoxysilane;chloropropyltriethoxysilane; chloropropyltrimethoxysilane;octadecyltrimethoxysilane; octadecyltriethoxysilane;octyltrimethoxysilane; octyltriethoxysilane;3,3.3-trifluoropropyltrimethoxysilane;3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; and3-cyanobutyltrimethoxysilane alone or in a mixture withtetraethoxysilane or tetramethoxysilane.

In another embodiment, the monomer is a substituted benzene, including(but not limited to) 1,4-bis(triethoxysilyl)benzene,1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene,1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene,1,3,5-tris(trimethoxysilyl)benzene, andbis(4-triethoxysilylphenyl)diethoxysilane.

In other embodiment, the porous inorganic/organic hybrid core asdescribed herein has been surface modified with a surface modifierhaving the formula Z_(a)(R′)_(b)Si—R″, where Z=Cl, Br, I, C₁-C₅ alkoxy,dialkylamino or trifluoromethanesulfonate; a and b are each an integerfrom 0 to 3 provided that a+b=3; R′ is a C1-C6 straight, cyclic orbranched alkyl group, and R″ is a functionalizing group.

In another embodiment, the hybrid core have been surface modified bycoating with a polymer.

In certain embodiments, R′ is selected from the group consisting ofmethyl, ethyl, propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl,isopentyl, hexyl and cyclohexyl. In other embodiments, R is selectedfrom the group consisting of alkyl, alkenyl, alkynyl, aryl, cyano,amino, diol, nitro, ester, a cation or anion exchange group, an alkyl oraryl group containing an embedded polar functionality and a chiralmoiety.

In one embodiment, R″ is a C₁-C₃₀ alkyl group. In a further embodiment,R″ comprises a chiral moiety. In another further embodiment, R″ is aC₁-C₂₀ alkyl group.

In certain embodiments, the surface modifier is selected from the groupconsisting of octyltrichlorosilane, octadecyltrichlorosilane,octyldimethylchlorosilane and octadecyldimethylchlorosilane.Advantageously, the surface modifier is selected from the groupconsisting of octyltrichlorosilane and octadecyltrichlorosilane.

In another embodiment, the hybrid core has been surface modified by acombination of organic group and silanol group modification.

In still another embodiment, the hybrid core has been surface modifiedby a combination of organic group modification and coating with apolymer. In a further embodiment, the organic group comprises a chiralmoiety.

In yet another embodiment, the hybrid core has been surface modified bya combination of silanol group modification and coating with a polymer.

In other embodiments, the hybrid core has been surface modified viaformation of an organic covalent bond between the particle's organicgroup and the modifying reagent.

In still other embodiments, the hybrid core has been surface modified bya combination of organic group modification, silanol group modificationand coating with a polymer.

In another embodiment, the hybrid core has been surface modified bysilanol group modification.

In certain embodiments, the porous inorganic/organic hybrid core is amonolith.

In another aspect, the invention provides materials as described hereinwherein the hybrid core further comprises a nanoparticle or a mixture ofmore than one nanoparticles dispersed within the hybrid core.

In certain embodiments, the nanoparticle is present in <20% by weight ofthe nanocomposite, <10% by weight of the nanocomposite, or <5% by weightof the nanocomposite.

In other embodiments, the nanoparticle is crystalline or amorphous andmay be silicon carbide, aluminum, diamond, cerium, carbon black, carbonnanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, oxides thereof, or a nitride thereof. In particular embodiments,the nanoparticle is a substance which comprises one or more moietiesselected from the group consisting of nanodiamonds, silicon carbide,titanium dioxide, cubic-boronitride. In certain embodiments thenanoparticle comprises a composite material, a magnetic material, a highthermal conductivity additive or a nanoparticle having a layeredstructure of additives.

In other embodiments, the nanoparticles may be less than or equal to 200nm in diameter, less than or equal to 100 nm in diameter, less than orequal to 50 nm in diameter, or less than or equal to 20 nm in diameter.

Porous Shell Layer Material

The materials of the invention have one or more layers of a porous shellmaterial applied to the substantially non-porous core. In certainembodiments, one or more layers of porous shell material are a porousinorganic/organic hybrid material; a porous silica or a porous compositematerial.

In certain aspects, the materials of the invention have a rough surface.In still other aspects, the materials of the invention have a smoothsurface. As used herein,

In certain embodiments, each porous layer is independently from 0.02 mto 5 μm. in thickness as measured perpendicular to the surface of thenonporous core.

In other embodiments, each porous layer is independently from 0.06 μm to1 μm. in thickness as measured perpendicular to the surface of thenonporous core.

In still other embodiments, each porous layer is independently from 0.20μm to 0.70 μm. in thickness as measured perpendicular to the surface ofthe nonporous core.

In certain embodiments, the materials of the invention have between 1and 15 layers of porous shell material. In other embodiments between 2and 5 layers of porous shell material. In still others 1 or 2 layers ofporous shell materials.

Porous Hybrids

In certain embodiments, the porous hybrid layer material or shellmaterial which may layered onto the hybrid core may be independentlyderived from

condensation of one or more polymeric organofunctional metal precursors,and/or polymeric metal oxide precursors on the surface of the hybridcore, or

application of partially condensed polymeric organofunctional metalprecursors, a mixture of two or more polymeric organofunctional metalprecursors, or a mixture of one or more polymeric organofunctional metalprecursors with a polymeric metal oxide precursors on the surface of thehybrid core.

In certain aspects, the inorganic portion of the surrounding material isindependently selected from the group consisting of alumina, silica,titania, cerium oxide, or zirconium oxides, and ceramic materials.

Alternatively, the hybrid layer material may independently derived from

condensation of one or more organofunctional silanes and/ortetraalkoxysilane on the surface of the hybrid core, or

application of partially condensed organofunctional silane, a mixture oftwo or more organofunctional silanes, or a mixture of one or moreorganofunctional silanes with a tetraalkoxysilane (i.e.,tetraethoxysilane, tetramethoxysilane) on the surface of the hybridcore.

In other aspects, the hybrid layer material may independently comprisefrom about 0-100 mol % hybrid material. The inorganic portion of thesurrounding material may independently be alumina, silica, titaniumoxide, cerium oxide, zirconium oxide or ceramic materials or a mixturethereof.

In specific aspects, the inorganic portion of the hybrid layer materialmay independently be present in an amount ranging from about 0 molar %to not more than about 25 molar %, wherein the pores of the surroundingmaterial are substantially disordered. Similarly, the inorganic portionof the surrounding material may independently be present in an amountranging from about 25 molar % to not more than about 50 molar %, whereinthe pores of the surrounding material are substantially disordered, andwherein the hybrid layer material may or may not independently possessesa chromatographically enhancing pore geometry (CEPG). In certainembodiments, the inorganic portion of the hybrid layer material mayindependently be present in an amount ranging from about 50 molar % tonot more than about 75 molar %, wherein the pores of the hybrid layermaterial are substantially disordered, and wherein the hybrid layermaterial independently possesses a chromatographically enhancing poregeometry (CEPG). In still other embodiments, the inorganic portion ofthe hybrid layer material may independently be present in an amountranging from about 75 molar % to not more than about 100 molar %,wherein the pores of the hybrid layer material are substantiallydisordered, and wherein the hybrid layer material may or may notindependently possesses a chromatographically enhancing pore geometry(CEPG).

In still other aspects, the inorganic portion of the hybrid layermaterial may independently be present in an amount ranging from about 0molar % to not more than about 100 molar %; specifically, 0%-10%, 0%-5%,0%-4%, 0%-3%, 0%-2%, 0%-1%, 1%-10%, 1%-5%, 1%-4%, 1%-3%, 1%-2%, 5%-100%,10%-100%, 15%-100%, 20%-100%, 25%-100%, 30%-100%, 35%-100%, 40%-100%,45%-100%, 55%-100%, 60%-100%, 65%-100%, 70%-100%, 75%-100%, 80%-100%,81%-100%, 82%-100%, 83%-100%, 84%-100%, 85%-100%, 86%-100%, 87%-100%,88%-100%, 89%-100%, 90%-100%, 91%-100%, 92%-100%, 93%-100%, 94%-100%,95%-100%, 96%-100%, 97%-100%, 98%-100%, or 99%-100%.

In some aspects, the hybrid layer material may comprise a material offormula I:(SiO₂)_(d)/[R²((R)_(p)(R¹)_(q)SiO_(t))_(m)];  (I)wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

p and q are each independently 0.0 to 3.0;

t is 0.5, 1.0, or 1.5;

d is 0 to about 30;

m is an integer from 1-20; wherein R, R¹ and R² are optionallysubstituted; provided that:

(1) when R² is absent, m=1 and

${t = \frac{\left( {4 - \left( {p + q} \right)} \right)}{2}},$when 0<p+q≤3; and

(2) when R² is present, m=2-20 and

${t = \frac{\left( {3 - \left( {p + q} \right)} \right)}{2}},$when p+q≤2.

In other aspects, the hybrid layer material may comprise a material offormula II:(SiO₂)_(d)/[(R)_(p)(R¹)_(q)SiO_(t)]  (II);wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

d is 0 to about 30;

p and q are each independently 0.0 to 3.0, provided that when p+q=1 thent=1.5; when p+q=² then t=1; or when p+q=3 then t=0.5.

In still other aspects, the hybrid layer material may comprise amaterial of formula III:(SiO₂)_(d)/[R²((R¹)_(r)SiO_(t))m]  (III)wherein,

R¹ is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁—C heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl; R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl,C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl,C₁-C₁₈ heteroaryl; or absent; wherein each R² is attached to two or moresilicon atoms;

d is 0 to about 30;

r is 0, 1 or 2, provided that when r=0 then t=1.5; or when r=1 then t=1;or when r=2 then t=0.5; and

m is an integer from 1-20.

In yet aspects, the hybrid layer material may comprise a material offormula TV:(A)x(B)y(C)z  (IV),wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat unit which is bonded to one or more repeatunits B or C via an inorganic siloxane bond and which may be furtherbonded to one or more repeat units A or B via an organic bond;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+z=1. In certain embodiments, when z=0, then 0.002≤x/y≤210, and whenz≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In still yet other aspects, the hybrid layer material may comprise amaterial of formula V:(A)x(B)y(B*)y*(C)z  (V),wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat units which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond;

B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or B* or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+y*+z=1. In certain embodiments, when z=0, then 0.002≤x/(y+y*)≤210,and when z≠0, then 0.0003≤(y+y*)/z≤500 and 0.002≤x/(y+y*+z)≤210.

In certain aspects, R² in the formulas presented above may be present orabsent.

In certain aspects, R¹ in the formulas presented above is C₁-C₁₈ alkylgroup substituted by hydroxyl. In still other aspects, R¹ in theformulas presented above is hydroxypropyl. In still other aspects, thehydroxy substituted alkyl group is further functionalized by anisocyanate. In yet other aspects, the isocyanate is octadecylisocyanate, dodecyl isocyanate, pentafluorophenyl isocyanate,4-cyanophenyl isocyanate, 3-cyanophenyl isocyanate, 2-cyanophenylisocyanate, phenyl isocyate, benzyl isocyanate, phenethyl isocyanate ordiphenylethyl isocyante.

In certain embodiments, the organosiloxane is, without limitation,phenyltriethoxysilane; phenyltrimethoxysilane;phenylethyltriethoxysilane; phenylethyltrimethoxysilane;ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane;methyltrimethoxysilane diethyldiethoxysilane; diethyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(trimethoxysilyl)ethanc; 1,2-bis(methyldiethoxysilyl)ethane;1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane;vinyltrimethoxysilane; mercaptopropyltrimethoxysilane;mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene;1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane;1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(triethoxysilylethyl)benzene;1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane;hexyltrimethoxysilane; chloropropyltriethoxysilane;chloropropyltrimethoxysilane; octadecyltrimethoxysilane;octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane;3,3.3-trifluoropropyltrimethoxysilane;3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; and3-cyanobutyltrimethoxysilane alone or in a mixture withtetraethoxysilane or tetramethoxysilane.

In another embodiment, the organosiloxane is, without limitation, asubstituted benzene, including (but not limited to)1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene,1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene,1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene,and bis(4-triethoxysilylphenyl)diethoxysilane.

In another aspect, the invention provides materials as described hereinwherein the hybrid layer material further comprises a nanoparticle or amixture of more than one nanoparticles dispersed within the hybrid core.

In certain embodiments, the nanoparticle is present in <20% by weight ofthe nanocomposite, <10% by weight of the nanocomposite, or <5% by weightof the nanocomposite.

In other embodiments, the nanoparticle is crystalline or amorphous andmay be silicon carbide, aluminum, diamond, cerium, carbon black, carbonnanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, oxides thereof, or a nitride thereof. In particular embodiments,the nanoparticle is a substance which comprises one or more moietiesselected from the group consisting of nanodiamonds, silicon carbide,titanium dioxide, cubic-boronitride.

In other embodiments, the nanoparticles may be less than or equal to 200μm in diameter, less than or equal to 100 μm in diameter, less than orequal to 50 μm in diameter, or less than or equal to 20 μm in diameter.

Porous Silica

In certain embodiments, the porous shell layer materials are poroussilica.

Porous Composites.

In certain embodiments, the porous shell layer materials are compositematerials. Composite materials describe the engineered materials of theinvention composed of one or more components described herein incombination with dispersed nanoparticles, wherein eachcomponent/nanoparticle remains separate and distinct on a macroscopiclevel within the finished structure. The composite material of thepresent invention is independent of form, and may be monolithic orparticulate in nature. Moreover, the short-hand convention used hereinto describe a composite material containing a dispersed nanoparticle,Np/(A)_(w)(B)_(x)(C)_(y), may be understood as follows: the symbolicrepresentation to the left of the slash mark represents the dispersednanoparticle, and the symbolic representations to the right of the slashmark represent the components that comprise the material that thenanoparticle (noted on the left of the slash mark) is dispersed within.In certain embodiments, the composite materials of the present inventionmay be nanocomposites, which are known to include, at least, forexample, nano/nano-type, intra-type, inter-type, and intra/inter-type.(Nanocomposites Science and Technology, edited by P. M. Ajayan, L. S.Schadler, P. V. Braun, Wiley-VCH (Weinheim, Germany), 2003) The term“nanoparticle” is a microscopic particle/grain or microscopic member ofa powder/nanopowder with at least one dimension less than about 100 nm,e.g., a diameter or particle thickness of less than about 100 nm (0.1μm), which may be crystalline or noncrystalline.

Nanoparticles have properties different from, and often superior tothose of conventional bulk materials including, for example, greaterstrength, hardness, ductility, sinterability, and greater reactivityamong others. Considerable scientific study continues to be devoted todetermining the properties of nanomaterials, small amounts of which havebeen synthesized (mainly as nano-size powders) by a number of processesincluding colloidal precipitation, mechanical grinding, and gas-phasenucleation and growth. Extensive reviews have documented recentdevelopments in nano-phase materials, and are incorporated herein byreference thereto: Gleiter, H. (1989) “Nano-crystalline materials,”Prog. Mater. Sci. 33:223-315 and Siegel, R. W. (1993) “Synthesis andproperties of nano-phase materials,” Mater. Sci. Eng. A 168:189-197. Incertain embodiments, the nanoparticles comprise oxides or nitrides ofthe following: silicon carbide, aluminum, diamond, cerium, carbon black,carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, and mixtures thereof. In certain embodiments, the nanoparticlesof the present invention are selected from diamonds, zirconium oxide(amorphous, monoclinic, tetragonal and cubic forms), titanium oxide(amorphous, anatase, brookite and rutile forms), aluminum (amorphous,alpha, and gamma forms), and boronitride (cubic form). In particularembodiments, the nanoparticles of the present invention are selectedfrom nanodiamonds, silicon carbide, titanium dioxide (anatase form),cubic-boronitride, and any combination thereof. Moreover, in particularembodiments, the nanoparticles may be crystalline or amorphous. Inparticular embodiments, the nanoparticles are less than or equal to 100μm in diameter, e.g., less than or equal to 50 μm in diameter, e.g.,less than or equal to 20 μm in diameter.

Moreover, it should be understood that the nanoparticles that arecharacterized as dispersed within the composites of the invention areintended to describe exogenously added nanoparticles. This is incontrast to nanoparticles, or formations containing significantsimilarity with putative nanoparticles, that are capable of formation insitu, wherein, for example, macromolecular structures, such asparticles, may comprise an aggregation of these endogenously created.

Nanoparticles are of great scientific interest as they are effectively abridge between bulk materials and atomic or molecular structures. A bulkmaterial should have constant physical properties regardless of itssize, but at the nano-scale this is often not the case. Size-dependentproperties are observed such as quantum confinement in semiconductorparticles, surface plasmon resonance in some metal particles andsuperparamagnetism in magnetic materials.

In certain embodiments, the composite materials include magneticmaterials, materials having a high thermal conductivity, or mixturesthereof.

Materials having a high thermal conductivity, high thermal conductivitycores or a high thermal conductivity additive is defined as a material,core or additive used in a superficially porous particle having athermal conductivity greater than 20 W/(m·K). In various embodiments thecore or additive has a thermal conductivity ranges from: about 20W/(m·K) to not more than 3500 W/(m·K); about 100 W/(m·K) to not morethan 3300 W/(m·K); and 400 W/(m·K) to not more than 3000 W/(m·K). Thishigh thermal conductivity core or additive can be a 0.1-8 m coreparticle, nanoparticle additives, or a metal oxide precursor. In variousembodiments the high thermal conductivity core or additive includes (butis not limited to) aluminum, copper, gold, and diamonds.

A high thermal diffusivity additive is defined as an additive used in asuperficially porous particle having a thermal diffusivity greater than20 mm²/s. In various embodiments the additive has a thermal diffusivityranges from: about 20 mm²/s to not more than 2000 mm²/s; about 100 mm²/sto not more than 1600 mm²/s; and 150 mm²/s to not more than 1400 mm²/s.This high thermal conductivity additive can be a 0.1-8 m core particle,nanoparticle additives, or a metal oxide precursor. In variousembodiments the high thermal conductivity additive includes (but is notlimited to) aluminum, copper, gold, and diamonds.

A magnetic material include materials that have a mass magnetization (o,magnetic moment per unit mass, magnetic saturation or saturationmagnetization) at room temperature greater than 15 emu/g (A m²/kg). Thisincludes ferromagnetic and ferrimagnetic materials, including (but isnot limited to): magnetite (ferrous ferric oxide); maghemite; yttriumiron garnet, cobalt, CrO₂; and ferrites containing iron and Al, Mg, Ni,Zn, Mn or Co). Magnetic core particles do not include other oxides ofiron, including hematite and goethite, that have mass magnetizationvalues less than 10 emu/g. Hematite (0.4 emu/g) is consideredantiferromagnetic at room temperature.

Gradient Materials

In certain embodiments, the superficially porous materials of theinvention utilize core materials having an increased hybrid content nearthe surface of the core.

In other embodiments, the superficially porous material of the inventionutilize core materials having a decreased hybrid content near thesurface of the core.

In such cases, such increase or decrease generally occurs within 1-200nm of the surface of the core; alternatively within 5-60 nm of thesurface of the core.

Similarly, in certain embodiments, the superficially porous materials ofthe invention include superficially porous materials having an increasedhybrid content near the surface of the core. In other embodiments, thesuperficially porous material of the invention include superficiallyporous materials having a decreased hybrid content near the surface ofthe core.

In such cases, such increase or decrease generally occurs within 1-200nm of the surface of the superficially porous material; alternativelywithin 5-60 nm of the surface of the superficially porous material.

Core and Material Morphology

In certain embodiments, the superficially porous material of theinvention has specific core morphology. In certain embodiments, suchcore morphology is produced by using cores having the defined shape. Incertain other embodiments, the core morphology refers to the specificdefined shape of the product material of the invention.

In certain embodiments, the cores or the product material has a highlyspherical, rod shaped, bent-rod shaped, toroid shaped or dumbbell shapedcore morphology.

In certain other embodiments, the cores or the product material has amixture of highly spherical, rod shaped, bent-rod shaped, toroid shapedor dumbbell shaped core morphologies.

Core and Material Properties.

The superficially porous material of the invention have significantlyhigher thermal conductivity than fully porous silica particles of thesame size. In certain embodiments, the superficially porous material ofthe invention have significantly higher thermal conductivity thansuperficially porous silica particles of the same size. Determination ofparticle thermal conductivity can be made by the method of Gritti andGuiochon [J. Chromatogr. A, 2010, 1217, 5137) taking into accountdifferences in bulk material properties, pore volume, surfacemodification type and coverage.

The superficially porous material of the invention have significantlyimproved chemical stability when exposed to high pH mobile phasesunbonded, fully porous silica particles of the same size. In certainembodiments, the superficially porous material of the invention havesignificantly improved chemical stability when exposed to high pH mobilephases unbonded, superficially porous silica particles of the same size.

The superficially porous material of the invention are capable offorming a packed beds with improved permeability as compared to fullyporous silica particles of the same size. In certain embodiments, thesuperficially porous material of the invention are capable of forming apacked beds with improved permeability as compared to superficiallyporous silica particles of the same size. Improved permeability for agive particle size is observed as a decrease in column backpressure.Determination of permeability of packed beds can be made by inverse sizeexclusion chromatography.

The superficially porous materials (which are particles) have an averageparticle size of the material is between 0.8-3.0 μm. Specifically, theaverage particle size of the material may be between 1.1-2.9 μm orbetween 1.3-2.7 μm.

The superficially porous materials have pores which have an averagediameter of about 25-600 Å; about 60-350 Å; about 80-300 Å; or about90-150 Å.

The superficially porous materials have an average pore volume of about0.11-0.50 cm³/g; about 0.09-0.45 cm³/g; or about 0.17-0.30 cm³/g.

The superficially porous materials have a pore surface area betweenabout 10 m²/g and 400 m²/g.

Surface Modification

The materials of the invention may further be surface modified.

Thus, in one embodiment, the material as described herein may be surfacemodified with a surface modifier having the formula Z_(a)(R′)_(b)Si—R″,where Z=Cl, Br, I, C₁-C₅ alkoxy, dialkylamino ortrifluoromethanesulfonate; a and b are each an integer from 0 to 3provided that a+b=3; R′ is a C₁-C₆ straight, cyclic or branched alkylgroup, and R″ is a functionalizing group.

In another embodiment, the materials have been surface modified bycoating with a polymer.

In certain embodiments, R′ is selected from the group consisting ofmethyl, ethyl, propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl,isopentyl, hexyl and cyclohexyl. In other embodiments, R′ is selectedfrom the group consisting of alkyl, alkenyl, alkynyl, aryl, cyano,amino, diol, nitro, ester, a cation or anion exchange group, an alkyl oraryl group containing an embedded polar functionality and a chiralmoiety. In certain embodiments, R′ is selected from the group consistingof aromatic, phenylalkyl, fluoroaromatic, phenylhexyl,pentafluorophenylalkyl and chiral moieties.

In one embodiment, R″ is a C₁-C₃₀ alkyl group. In a further embodiment,R″ comprises a chiral moiety. In another further embodiment, R″ is aC₁-C₂₀ alkyl group.

In certain embodiments, the surface modifier comprises an embedded polarfunctionality. In certain embodiments, such embedded polar functionalityincludes carbonate, amide, urea, ether, thioether, sulfinyl, sulfoxide,sulfonyl, thiourea, thiocarbonate, thiocarbamate, ethylene glycol,heterocyclic, or triazole functionalities. In other embodiments, suchembedded polar functionality includes carbamate functionalities such asdisclosed in U.S. Pat. No. 5,374,755, and chiral moieties. Such groupsinclude those of the general formula

wherein l, m, o, r and s are 0 or 1, n is 0, 1, 2 or 3 p is 0, 1, 2, 3or 4 and q is an integer from 0 to 19; R₃ is selected from the groupconsisting of hydrogen, alkyl, cyano and phenyl; and Z, R′, a and b aredefined as above. Advantageously, the carbamate functionality has thegeneral structure indicated below:

wherein R⁵ may be, e.g., cyanoalkyl, t-butyl, butyl, octyl, dodecyl,tetradecyl, octadecyl, or benzyl. Advantageously, R⁵ is octyl, dodecyl,or octadecyl.

In certain embodiments, the surface modifier is selected from the groupconsisting of phenylhexyltrichlorosilane,pentafluorophenylpropyltrichlorosilane, octyltrichlorosilane,octadecyltrichlorosilane, octyldimethylchlorosilane andoctadecyldimethylchlorosilane. In some embodiments, the surface modifieris selected from the group consisting of octyltrichlorosilane andoctadecyltrichlorosilane. In other embodiments, the surface modifier isselected from the group consisting of an isocyanate or1,1′-carbonyldiimidazole (particularly when the hybrid group contains a(CH₂)₃OH group).

In another embodiment, the material has been surface modified by acombination of organic group and silanol group modification.

In still another embodiment, the material has been surface modified by acombination of organic group modification and coating with a polymer. Ina further embodiment, the organic group comprises a chiral moiety.

In yet another embodiment, the material has been surface modified by acombination of silanol group modification and coating with a polymer.

In other embodiments, the material has been surface modified viaformation of an organic covalent bond between the particle's organicgroup and the modifying reagent.

In still other embodiments, the material has been surface modified by acombination of organic group modification, silanol group modificationand coating with a polymer.

In another embodiment, the material has been surface modified by silanolgroup modification.

Approaches to Synthesis

The invention provides a method for preparing a superficially porousmaterial comprising:

-   -   a.) providing a substantially nonporous core material; and    -   b.) applying to said core material one or more layers of porous        shell material to form a superficially porous material

In certain embodiments, the method further provides the step of:

-   -   c.) optimizing one or more properties of the superficially        porous material.

The approaches described herein allows for the synthesis of narrowparticle size distribution fully porous, spherical particles as well asnarrow particle size distribution superficially porous (defined as aporous shell layer on a nonporous core particle) particles having achromatographically enhanced pore geometry. The processes involves thecondensation of a tetraalkoxysilane (e.g., tetraethoxysilane ortetramethoxysilane) alone or co-condensed with a second organosilanethrough modification of a traditional Stöber-growth process. Listedbelow are non-limiting descriptions of this process.

Method A:

Step 1) Condensation of a tetraalkoxysilane with or without(R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) to form seed particles (0.2-10 μm)in the presence or absence of surfactants or pore structuring agents(including pore expanding molecules and polymers).

Step 2) Grow seed particles by condensation of a tetraalkoxysilane withor without (R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) to form larger coreparticles (0.3-20 μm) in the presence or absence of surfactants or porestructuring agents (including pore expanding molecules and polymers).Step 3) Further grow particles by co-condensation of a tetraalkoxysilanewith (R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) to yield non-porous particles(0.4-20 μm) in the presence or absence of surfactants or porestructuring agents (including pore expanding molecules and polymers).Step 4) Improve particle size distribution through particleclassification techniquesStep 5) Produce a porous silica particle by removal of organic group andor surfactants by thermal treatment.Step 6) Pore structure modification using fluorine containing chemicaltechniques, including ammonium bifluoride and hydrofluoric acid.Step 7) Pore structure modification by hydrothermal processing in thepresence or absence of surfactants or pore structuring agents (includingpore expanding molecules and polymers).Step 8) Improve particle size distribution through particleclassification techniques.Step 9) Use of elevated temperature treatment (>600° C.) to improveparticle mechanical stability.Step 10) Prepare the particle surface for modification by acid treatment(e.g., hydrochloric acid or hydrofluoric acid).Step 11) Chemical modification of the particle surfaceMethod B:Step 1) Condensation of a tetraalkoxysilane with or without(R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) to form seed particles (0.2-10 μm)in the presence or absence of surfactants or pore structuring agents.Step 2) Grow seed particles by condensation of a tetraalkoxysilane withor without (R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) to form larger coreparticles (0.3-20 μm) in the presence or absence of surfactants or porestructuring agents.Step 3) Further grow particles by co-condensation of a tetraalkoxysilanewith (R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) to yield non-porous particles(0.4-20 μm) in the presence or absence of surfactants or porestructuring agents (including pore expanding molecules and polymers).Step 4) Improve particle size distribution through particleclassification techniquesStep 5) Produce a porous silica particle by removal of organic groupand/or surfactants by thermal treatment or extraction techniques.Step 6) Pore structure modification using fluorine containing chemicaltechniques, including ammonium bifluoride and hydrofluoric acid.Step 7) Pore structure modification by pseudomorphic transformation inthe presence of surfactants and/or pore structuring agents (includingpore expanding molecules and polymers).Step 8) Surfactant removal by extraction techniques or by calcination.Step 9) Pore structure modification by hydrothermal processing in thepresence or absence of surfactants or pore structuring agents (includingpore expanding molecules and polymers).Step 10) Improve particle size distribution through particleclassification techniquesStep 11) Use of elevated temperature treatment (>600° C.) to improveparticle mechanical stability.Step 12) Prepare the particle surface for modification by acid treatment(e.g., hydrochloric acid or hydrofluoric acid).Step 13) Chemical modification of the particle surfaceMethod C (Specific Version of Method A):Step 1) Condensation of Si(OCH₂CH₃)₄ to form seed particles (0.2-2 μm)Step 2) Grow seed particles by condensation of Si(OCH₂CH₃)₄ to form alarger core particle (0.3-7 μm).Step 3) Further grow particles by co-condensation of Si(OCH₂CH₃)₄ withRSi(OR′)₃ (R=octyl or octadecyl and R′ is methyl or ethyl) to yieldnon-porous particle (0.4-10 μm) in the presence or absence of a porestructuring agent (e.g., mesitylene or an alkane). Here R=octyl oroctadecyl and R¹ is methyl or ethyl.Step 4) Improve particle size distribution through particleclassification techniquesStep 5) Produce a porous silica particle by removal of organic group bythermal treatment (500-600° C. in air).Step 6) Pore structure modification using ammonium bifluoride (4-20hours, 25-60° C.).Step 7) Pore structure modification by hydrothermal processing (7-20hours, pH 5-7, 90-150° C.).Step 8) Improve particle size distribution through particleclassification techniquesStep 9) Use of elevated temperature treatment (800-1,000° C.) to improveparticle mechanical stability.Step 10) Prepare the particle surface for modification usinghydrofluoric acid treatment.Step 11) Chemical modification of the particle surface usingchlorosilanes coupling and endcapping protocols.Method D (Modified Core Particle):Step 1) <10 μm particles (e.g., diamonds, zirconia, titania, ironoxides, cerium, cobalt, cobalt oxides, carbon, silica, silica carbide)are surface activated through treatment with acid, base, chemicalreduction, chemical oxidation, or through attachment of a surfacemodifying group (e.g., adsorption of an amine, surfactant, silane bond).Step 2) Particles are grown by condensation of a tetraalkoxysilane withor without (R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) in the presence orabsence of surfactants or pore structuring agents (including poreexpanding molecules and polymers).Step 3) Particle are further grown by co-condensation of atetraalkoxysilane with (R¹)_(a)(R²)_(b)(R³)_(c)Si(OR⁴)_(d) to yield anon-porous particles in the presence or absence of surfactants or porestructuring agents (including pore expanding molecules and polymers).Step 4) Improve particle size distribution through particleclassification techniquesStep 5) Produce a porous silica particle by removal of organic groupand/or surfactants by thermal treatment or extraction techniques.Step 6) Pore structure modification using fluorine containing chemicaltechniques, including ammonium bifluoride and hydrofluoric acid.Step 7) Pore structure modification by pseudomorphic transformation inthe presence of surfactants and/or pore structuring agents (includingpore expanding molecules and polymers).Step 8) Surfactant removal by extraction techniques or by calcination.Step 9) Pore structure modification by hydrothermal processing in thepresence or absence of surfactants or pore structuring agents (includingpore expanding molecules and polymers).Step 10) Improve particle size distribution through particleclassification techniquesStep 11) Use of elevated temperature treatment (>600° C.) to improveparticle mechanical stability.Step 12) Prepare the particle surface for modification by acid treatment(e.g., hydrochloric acid or hydrofluoric acid).Step 13) Chemical modification of the particle surfaceAlternatives

Many alternatives within a Method A-D can be explored. For example, ifparticle are substantially uniform in size after growth, further sizingsteps may not be required. Other steps that may be avoided are the useof fluorine containing chemical modification step before pseudomorphictransformation, or the use of a higher temperature treatment to improveparticle mechanical stability if the particles already have sufficientmechanical strength without the use of this step.

Method D may be useful for preparing superficially porous magneticparticles.

Other Approaches which Will be Useful in the Methods of the Inventionare as Follows.

In one aspect, the invention provides a method for preparing asuperficially porous material comprising:

-   -   a.) providing a substantially nonporous hybrid core material;        and    -   b.) applying to said core material one or more layers of porous        shell material to form a superficially porous material

In certain embodiments, the method for preparing a superficially porousmaterial further comprises the step of:

-   -   c.) optimizing one or more properties of the superficially        porous material.

In other embodiments, each layer of porous shell material wherein eachlayer is independently selected from is a porous inorganic/organichybrid material, a porous silica, a porous composite material ormixtures thereof.

In still other embodiments, each layer of porous shell material isapplied using sols, a polyelectrolyte or a chemically degradablepolymer, wherein:

a) the sols are inorganic sols, hybrid sols, nanoparticles, or mixturesthereof; and

b) the polyelectrolyte or chemically degradable polymer is removed fromthe material using chemical extraction, degradation, or thermaltreatment at temperatures less than 500° C., or combinations thereof.

In certain embodiments, each layer of porous shell material is appliedby formation through an electrostatic or acid/base interaction of anionizable group comprising the steps of:

-   -   a) pretreating or prebonding the substantially nonporous core        with an alkoxysilane that has an ionizable group,    -   b) treating the substantially nonporous core to sols that are        inorganic, hybrid, nanoparticle, or mixtures thereof, that have        been prebonded with an alkoxysilane that has an ionizable group        of the opposite charge to the ionizable group on the surface of        the core; and    -   c) forming additional layers on the material with sols that are        inorganic, hybrid, nanoparticle, or mixtures thereof that have        been prebonded with an alkoxysilant that has an ionizable group        of opposite charge to the ionizable group of prior layer.

In particular embodiments, the pretreatment of the substantiallynonporous core or sols includes washing with and acid or base, or acharged polyelectrolyte. In other embodiments, the pretreatment of thesubstantially nonporous core or sols includes chemical transformation ofan accessible hybrid organic group.

In still other embodiments the accessible hybrid organic group is anaromatic group that can undergo sulfonation, nitration, amination, orchloromethylation followed by oxidation or nucleophillic displacementwith amine containing groups to form ionizable groups. In yet otherembodiments, the accessible hybrid organic group is an alkene group thatcan undergo oxidation, cross-metathesis, or polymerization to formionizable groups. In specific embodiments, the accessible hybrid organicgroup is an thiol group that can undergo oxidation, radical addition,nucleophillic displacement, or polymerization to form ionizable groups.

In yet other embodiments, the prebonding of the substantially nonporouscore or sols includes bonding with an alkoxysilane that has an ionizablegroup of equation 1,R(CH₂)_(n)Si(Y)_(3-x)(R′)_(x)  (equation 1)where n=1-30, advantageously 2-3;x is 0-3; advantageously 0;Y represents chlorine, dimethylamino, triflate, methoxy, ethoxy, or alonger chain alkoxy group;R represent a basic group, including (but not limited to) —NH₂, —N(R′)H,—N(R′)₂, —N(R′)₃ ⁺, —NH(CH₂)_(m)NH₂, —NH(CH₂)_(m)N(R′)H,—NH(CH₂)_(m)N(R′)₂, —NH(CH₂)_(m)N(R′)₃ ⁺, pyridyl, imidizoyl, polyamine.R′ independently represents an alkyl, branched alkyl, aryl, orcycloalkyl group;m is 2-6.

In still yet other embodiments, the prebonding of the substantiallynonporous core or sols includes bonding with an alkoxysilane that has anionizable group of equation 2,A(CH₂)_(n)Si(Y)_(3-x)(R′)_(x)  (equation 2)where n=1-30, advantageously 2-3;x is 0-3; advantageously 0;Y represents chlorine, dimethylamino, triflate, methoxy, ethoxy, or alonger chain alkoxy group;A represent an acidic group, including (but not limited to) a sulfonicacid, carboxylic acid, phosphoric acid, boronic acid, arylsulfonic acid,arylcarboxylic acid, arylphosphonic acid, and arylboronic acid.R′ independently represents an alkyl, branched alkyl, aryl, orcycloalkyl group.

In particular embodiments, each layer of porous shell material isapplied using a polyelectrolyte or a chemically degradable polymer.

In other embodiments, the polyelectrolyte or a chemically degradable isremoved from the material by chemical extraction, degradation, orthermal treatment at temperatures less than 500° C., or combinationsthereof.

In certain embodiments, each layer of porous shell material is appliedusing alkoxysilanes, organoalkoxysilanes, nanoparticles,polyorganoalkoxysiloxanes, or combinations thereof, comprising the stepsof:

-   -   a) condensing siloxane precursors on the substantially        nonporoous core in a reaction mixture comprising ethanol, water        and ammonium hydroxide and optionally containing a non-ionic        surfactant, an ionic surfactant, a polyelectrolyte or a polymer        to form the porous shell material; and    -   b) introducing porosity is introduced through extraction,        degradation, oxidation, hydrolysis, deprotection, or        transformation of the hybrid group, ionic surfactant or        non-ionic surfactant or a combination thereof.

In particular embodiments, the alkoxysilanes, organoalkoxysilanes,nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof, arecondensed on the substantially nonporous core in a solution comprisingethanol, water, ammonium hydroxide, an ionic surfactant; and annon-ionic surfactant.

In other embodiments, the ionic surfactant is C₁₀-C₃₀N(R)₃ ⁺X⁻, where Ris methyl, ethyl, propyl, alkyl, fluoroalkyl; X is a halogen, hydroxide,or of the form R′SO₃ ⁻ or R′CO₂ ⁻ where R′ is methyl, ethyl, butyl,propyl, isopropyl, tert-butyl, aryl, tolyl, a haloalkyl or a fluoroalkylgroup.

In yet other embodiments, the ionic surfactant isoctadecyltrimethylanmnonium bromide, octadecyltrimethylammoniumchloride, hexadecyltrimethylammonium bromide, hexadecyltrimethylammoniumchloride, dodecyltrimethylammonium bromide, or dodecyltrimethylammoniumchloride.

In particular embodiments, the concentration of ionic surfactant ismaintained in the reaction solution between 5-17 mM; or in certainembodiments between 8-14 mM.

In other embodiments, the non-ionic surfactant is a diblock or triblockcopolymer. In certain embodiments, the copolymer is (PEO)x(PPO)y(PEO)x,

wherein

PEO is a polyethylene oxide repeat unit,

PPO is a polypropylene oxide repeat unit,

x is an integer between 5-106,

y is an integer between 30-85.

In particular embodiments the triblock copolymer is Pluronic® P123,having (PEO)₂₀(PPO)₇₀(PEO)₂₀. In still other embodiments, thealkoxysilanes, organoalkoxysilanes, or combinations thereof, arecondensed on the substantially nonporous core in a solution comprising:

ethanol, water, ammonium hydroxide or combinations thereof;

octadecyltrimethylammonium bromide; and

Pluronic® P123.

In certain embodiments, the alkoxysilane used is selected from the groupof tetramethoxsilane or tetraethoxysilane.

In still other embodiments, the organosiloxane is selected from thegroup of phenyltriethoxysilane; phenyltrimethoxysilane;phenylethyltriethoxysilane; phenylethyltrimethoxysilane;ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane;methyltrimethoxysilane, diethyldiethoxysilane; diethyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(trimethoxysilyl)ethane; 2-bis(triethoxysilyl)ethane;1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane;vinyltriethoxysilane; vinyltrimethoxysilane;mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane;1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene;1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane;1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(triethoxysilylethyl)benzene; or1,3-bis(trimethoxysilylethyl)benzene.

In yet other embodiments, the alkoxysilane used is tetraethoxysilane andthe organoalkoxysilane used is 1,2-bis(triethoxysilyl)ethane.

In certain other embodiments, the concentration ofoctadecyltrimethylammonium bromide is maintained between 8-14 mM.

In certain other embodiments, the molar ratio ofoctadecyltrimethylammonium bromide and Pluronic® P123 is maintained ator above 1.30.

In still other embodiments, the molar ratio of alkoxysilane toorganoalkoxysilane ranges between 30:1 to 1:30.

In certain embodiments, alkoxysilane, organoalkoxysilane, orcombinations thereof are prediluted in ethanol. In certain suchembodiments, prediluted ethanol solutions of alkoxysilane,organoalkoxysilane, or combinations thereof are added at a slow andconstant rate to prevent fines generation, aggregation andagglomeration. In other such embodiments, prediluted ethanol solutionsof alkoxysilane, organoalkoxysilane, or combinations thereof are added arate between 5-500 μL/min.

In other embodiments, a secondary solution comprising ethanol, water,ammonium hydroxide, ionic surfactant and non-ionic surfactant is addedat a slow and constant rate to prevent fines generation, aggregation andagglomeration. In certain such embodiments the secondary solutioncomprising ethanol, water, ammonium hydroxide, ionic surfactant andnon-ionic surfactant is added within a range between the rate requiredto maintain a uniform ratio of particle surface area (m²) to reactionvolume, to the rate required to maintain a uniform ratio of particlevolume (m³) to reaction volume.

In certain embodiments, the surfactant mixture is removed through one ormore of the following; extractions with acid, water, or organic solvent;ozonolysis treatments, thermal treatments <500° C., or thermaltreatments between 500-1000° C.

In still other embodiments, the surfactant mixture is removed throughcombination of acid extractions and ozonolysis treatments.

In certain embodiments, each layer of porous shell material is appliedusing alkoxysilanes, organoalkoxysilanes, nanoparticles,polyorganoalkoxysiloxanes, or combinations thereof: comprising the stepsof:

-   -   a) condensing siloxane precursors on the substantially        nonporoous core in a reaction mixture comprising ethanol, water        or ammonium hydroxide to form a non-porous hybrid        inorganic/organic shell material; and    -   b) introducing porosity is introduced through extraction,        degradation, oxidation, hydrolysis, deprotection, or        transformation of the hybrid group or a combination thereof.

In some such embodiments, the alkoxysilane used is selected from thegroup of tetramethoxsilane or tetraethoxysilane.

In other such embodiments, the organosiloxane is selected as one or moreof the following from the group of phenyltriethoxysilane;phenyltrimethoxysilane; phenylethyltriethoxysilane;phenylethyltrimethoxysilane; ethyltriethoxysilane;ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane,diethyldiethoxysilane; diethyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(trimethoxysilyl)ethane; 1,2-bis(triethoxysilyl)ethane;1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane;vinyltriethoxysilane; vinyltrimethoxysilane;mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane;1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene;1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane;1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(triethoxysilylethyl)benzene; or1,3-bis(trimethoxysilylethyl)benzene, octadecyltrimethoxysilane,octadecyltriethoxysilane, octyltrimethoxysilane, octyltriethoxysilane,dodecyltrimethoxysilane, and dodecyltriethoxysilane.

In still other such embodiments, the alkoxysilane used istetraethoxysilane and the organoalkoxysilane used isoctadecyltrimethoxysilane.

In certain such embodiments, the alkoxysilane, one or moreorganoalkoxysilanes, or combinations thereof are prediluted in ethanol.

In some such embodiments, the prediluted ethanol solutions ofalkoxysilane, one or more organoalkoxysilanse, or combinations thereofare added a slow and constant rate to prevent fines generation,aggregation and agglomeration.

In other such embodiments, prediluted ethanol solutions of alkoxysilane,one or more organoalkoxysilanes, or combinations thereof are added arate between 5-500 μL/min.

In certain embodiments, a secondary solution comprising ethanol, water,and ammonium hydroxide is added at a slow and constant rate to preventfines generation, aggregation and agglomeration.

In certain other embodiments, a secondary solution comprising ethanol,water, and ammonium hydroxide is added within a range between the raterequired to maintain a uniform ratio of particle surface area (m²) toreaction volume, to the rate required to maintain a uniform ratio ofparticle volume (m³) to reaction volume.

In certain embodiments, porosity is introduced through extraction,degradation, hydrolysis, deprotection, or transformation of the hybridgroup through one or more of the following; extractions with acid,water, or organic solvent; ozonolysis treatments, thermal treatments<500° C., or thermal treatments between 500-1000° C.

In still other embodiments, porosity is introduced through extraction,degradation, hydrolysis, deprotection, or transformation of the hybridgroup through combination of acid extractions, ozonolysis treatmentsand/or thermal treatments <500° C.

In certain embodiments, each layer is applied using a mixture of formulaXX.(D)_(d)(E)_(e)(F)_(f)  (Formula XX)wherein,

a) d+e+f=1

b) D is one or more inorganic components upon initial condensation.

c) E is one or more hybrid components upon initial condensation.

d) F is one or more hybrid components upon initial condensation that canbe further reacted to increase the porosity of the superficially porouslayer

In certain such embodiments, the precursor for the inorganic componentupon initial condensation (D) is selected from oxide, hydroxide,ethoxide, methoxide, propoxide, isopropoxide, butoxide, sec-butoxide,tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide,2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate,nitrate, chlorides, and mixtures thereof of silicon, titanium,zirconium, or aluminum.

In other such embodiments, the precursor for the inorganic componentupon initial condensation (D) is selected from tetraethoxysilane,tetramethoxysilane, methyl titanium triisopropoxide, methyl titaniumtriphenoxide, titanium allylacetoacetatetriisopropoxide, titaniummethacrylate triisopropoxide, titanium methacryloxyethylacetoacetatetriisopropoxide, pentamethylcyclopentadienyl titanium trimethoxide,pentamethylcyclopentadienyl titanium trichloride, and zirconiummethacryloxyethylacetoacetate tri-n-propoxide.

In still other such embodiments, the precursor for the hybrid componentupon initial condensation (E) is selected from1,2-bis(triethoxysilyl)ethane, 1,2-bis(trimethoxysilyl)ethane,1,4-bis(triethoxysilyl) benzene, 1,4-bis(trimethoxysilyl)benzene,1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene,1,3,5-tris(triethoxysilyl)benzene, 1,3,5-tris(trimethoxysilyl)benzene,and bis(4-triethoxysilylphenyl)diethoxysilane.

In yet other such embodiments, the precursor for the hybrid componentupon initial condensation that can be further reacted to increase theporosity of the superficially porous layer (F) is selected fromphenyltrimethoxysilane, phenyltriethoxysilane,acetyloxyethyltrimethoxysilane; acetyloxyethyltriethoxysilane;chloroethyltriethoxysilane; chloroethyltrimethoxysilane;methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane;bromoethyltrimethoxysilane; bromoethyltriethoxysilane;fluorotriethoxysilane; fluorotrimethoxysilane; and alkoxysilanes of thetype:(CH₃CH₂O)_(4-v)Si(OR*)_(v)  (Formula XXb)wherein

R* was the corresponding octadecyl, dodecyl, octyl, 2-ethoxyethyl, or3-ethyl-3-pentyl group,

v was an integer equal to 1-4,

In such embodiments, porosity is introduced by reaction of hybrid groupF through protodesilylation, hydrolysis, deprotection, acid extraction,thermal treatment <500° C., oxidation, ozonolysis or decomposition.

Another aspect of the invention provides, a method to produce a hybridcore with increased hybrid content near the surface of the core bymodifying a nonporous silica core with one more or more layers formedusing an organosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

Still another aspect of the invention provides, a method to produce asuperficially porous hybrid material that has increased hybrid contentnear the external surface of the material by modifying a superficiallyporous material with one more or more layers formed using anorganosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

Yet another aspect of the invention provides, a method to produce asuperficially porous hybrid particle that has increased hybrid contentnear the external surface of the particle by modifying a superficiallyporous particle with one more or more layers formed using anorganosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

Still another aspect of the invention provides, a method to produce asuperficially porous hybrid particle that has increased hybrid contentnear the external surface of the particle by modifying a superficiallyporous particle that is substantially silica (>90 molar %) with one moreor more layers formed using an organosiloxane, a mixture oforganosiloxane and alkoxysilane, polyorganoalkoxysilanes, a hybridinorganic/organic surrounding material, or combination thereof.

Still yet another aspect of the invention provides, a method to producea superficially porous hybrid particle that has increased hybrid contentnear the external surface of the particle comprising the steps of

a.) forming a superficially porous particle that is substantially silica(>90 molar %) and has a pore volume between 0.18-0.50 cm³/g; and

b.) reducing the porosity of this particle by 0.01-0.20 cm³/g by modifythis particle with one more or more layers formed using anorganosiloxane, a mixture of organosiloxane and alkoxysilane,polyorganoalkoxysilanes, a hybrid inorganic/organic surroundingmaterial, or combination thereof.

In certain embodiments of the invention, the methods provide materialsin which 1-15 layers are formed in the process. In other aspects, 2-5layers are formed. In still other 1-2 layers are formed.

In certain embodiments of the invention the superficially porousmaterial is optimized by acid extraction, classification, ozonolysistreatment, hydrothermal treatment, acid treatment or combinationsthereof.

In yet other embodiments of the invention, the superficially porousmaterial is further surface modified. In some aspects by: coating with apolymer; coating with a polymer by a combination of organic group andsilanol group modification; a combination of organic group modificationand coating with a polymer; a combination of silanol group modificationand coating with a polymer; formation of an organic covalent bondbetween the material's organic group and a modifying reagent; or acombination of organic group modification, silanol group modificationand coating with a polymer.

In another aspect, the invention provides a method for increasing theporosity of a substantially nonporous material comprising:

-   -   a.) providing a substantially nonporous core material; and    -   b.) applying to said core material one or more layers of porous        shell material to form a superficially porous material.

In such methods of increasing the porosity of a substantially nonporousmaterial, the methods of applying to said core material one or morelayers of porous shell material will be understood to be substantiallythe same as those described above for preparing a superficially porousmaterial and should be considered as such.

Separation Devices and Kits

Another aspect provides a variety of separations devices having astationary phase comprising the materials as described herein. Theseparations devices include, e.g., chromatographic columns, thin layerplates, filtration membranes, sample cleanup devices and microtiterplates; packings for HPLC columns; solid phase extraction (SPE);ion-exchange chromatography; magnetic bead applications; affinitychromatographic and SPE sorbents; sequestering reagents; solid supportsfor combinatorial chemistry; solid supports for oligosaccharide,polypeptides, and/or oligonucleotide synthesis; solid supportedbiological assays; capillary biological assay devices for massspectrometry, templates for controlled large pore polymer films;capillary chromatography; electrokinetic pump packing materials; packingmaterials for microfluidic devices; polymer additives; catalysissupports; and packings materials for microchip separation devices.Similarly, materials of the invention can be packed into prepartory,microbore, capillary, and microfluidic devices.

The materials of the invention impart to these devices improvedlifetimes because of their improved stability. Thus, in a particularaspect, the invention provides a chromatographic column having improvedlifetime, comprising

a) a column having a cylindrical interior for accepting a packingmaterial, and

b) a packed chromatographic bed comprising a materials as describedherein.

I another particular aspect, the invention provides a chromatographicdevice, comprising

a) an interior channel for accepting a packing material and

b) a packed chromatographic bed comprising a materials as describedherein.

The invention also provides for a kit comprising the materials asdescribed herein, as described herein, and instructions for use. In oneembodiment, the instructions are for use with a separations device,e.g., chromatographic columns, thin layer plates, filtration membranes,sample cleanup devices, solid phase extraction device, microfluidicdevice, and microtiter plates.

EXAMPLES

The present invention may be further illustrated by the followingnon-limiting examples describing the chromatographic materials.

Materials

All reagents were used as received unless otherwise noted. Those skilledin the art will recognize that equivalents of the following supplies andsuppliers exist and, as such, the suppliers listed below are not to beconstrued as limiting.

Characterization

Those skilled in the art will recognize that equivalents of thefollowing instruments and suppliers exist and, as such, the instrumentslisted below are not to be construed as limiting. The % C, % H, % Nvalues were measured by combustion analysis (CE-440 Elemental Analyzer;Exeter Analytical Inc., North Chelmsford, Mass.) or % C by CoulometricCarbon Analyzer (modules CM5300, CM5014, UIC Inc., Joliet, Ill.). Thespecific surface areas (SSA), specific pore volumes (SPV) and theaverage pore diameters (APD) of these materials were measured using themulti-point N₂ sorption method (Micromeritics ASAP 2400; MicromeriticsInstruments Inc., Norcross, Ga.). The SSA was calculated using the BETmethod, the SPV was the single point value determined for P/P₀>0.98 andthe APD was calculated from the desorption leg of the isotherm using theBJH method. Scanning electron microscopic (SEM) image analyses wereperformed (JEOL JSM-5600 instrument, Tokyo, Japan) at 7 kV. Focused ionbeam scanning electron microscopic (FEB/SEM) image analyses wereperformed by Analytical Answers Inc. (Woburn, Mass.) on an FEI Model 200Focused Ion Beam instrument, and a Hitachi S4800 Ultra-Field emissionSEM. Particle sizes were measured using a Beckman Coulter Multisizer 3analyzer (30 μm aperture, 70,000 counts; Miami, Fla.). The particlediameter (dp) was measured as the 50% cumulative diameter of the volumebased particle size distribution. The width of the distribution wasmeasured as the 90% cumulative volume diameter divided by the 10%cumulative volume diameter (denoted 90/10 ratio). Light scatteringparticle size measurements were measured using a Malvern Mastersizer2000 in water. Zeta-potential measurements were made using a MalvernZetaSizer NanoSeries (model ZEN3600). Multinuclear (¹³C, ²⁹Si) CP-MASNMR spectra were obtained using a Bruker Instruments Avance-300spectrometer (7 mm double broadband probe). The spinning speed wastypically 5.0-6.5 kHz, recycle delay was 5 sec. and thecross-polarization contact time was 6 msec. Reported ¹³C and ²⁹Si CP-MASNMR spectral shifts were recorded relative to tetramethylsilane usingthe external standards adamantane (¹³C CP-MAS NMR, δ 38.55) andhexamethylcyclotrisiloxane (²⁹Si CP-MAS NMR, 6-9.62). Populations ofdifferent silicon environments were evaluated by spectral deconvolutionusing DMFit software. [Massiot, D.; Fayon, F.; Capron, M.; King, I.; LeCalvé, S.; Alonso, B.; Durand, J.-O.; Bujoli, B.; Gan, Z.; Hoatson, G.Magn. Reson. Chem. 2002, 40, 70-76]. Classification techniques aredescribed, for example, in W. Gerhartz, et al. (editors) Ullmann'sEncyclopedia of Industrial Chemistry, 5^(th) edition, Volume B2: UnitOperations I, VCH Verlagsgesellschaft mbH, (Weinheim, Fed. Rep. Germ.1988). Magnetic measurements were made using a vibrating samplemagnetometer (ADE/DMS Model 880) by ArKival Technology Corporation(Nashua, N.H.). Phase characterization were made by Wide Angle X-RayPowder Diffraction (XRPD) analysis (H&M Analytical Services, Inc.Allentown, N.J.), using a Bruker D4 diffractometer (Cu radiation at 40KV/30 mA). Scans were run over the angular range of 10° to 90° 2-Thetawith a step size of 0.02° and a counting time of 715 seconds per step.

Example 1

Nonporous hybrid particles were formed following a modification of areported process {Choi, J. Y.; Kim, C. H.; Kim, D. K. J. Am. Ceram.Soc., 1998, 81, 1184-1188. Seog, 1. S; Kim, C. H. J. Mat. Sci., 1993,28, 3277-3282}. To a clean 40 ml, vial was added a stir bar, water (26mL) and 14.8 M NH₄OH (4.3 mL). This solution was then heated to 60° C.with stirring (600 rpm) in a water bath before one or morealkoxysilanes, including phenyltriethoxysilane (PTES, Gelest,Morrisville, Pa.), 1,8-bis(triethoxysilyl)octane (BTEO, Gelest,Morrisville, Pa.), 1,2-bis(triethoxysilyl)ethane (BTEE, Gelest,Morrisville, Pa.), 1,2-bis(methyldiethoxysilyl)ethane (BMDEE, Gelest,Morrisville, Pa.), vinyltriethoxysilane (VTES, Gelest, Morrisville,Pa.), or mercaptopropyltrimethoxysilane (MPTMS, Lancaster Chemical,Lancaster UK) were added (3 mL total). The reaction was sealed, andreturned to the 60° C. water bath for 2 h. The reaction was furthercontinued for 24 h at 25° C. The particles were isolated by repeatedcentrifugation from water (3×40 mL) and then ethanol (3×40 mL). Theparticles were then air dried for 12 h and vacuum dried (70° C., 30 mmHg) for 24 h. Carbon content was determined by combustion analysis.Average particle size was determined by SEM. These experiments differfrom the prior reports in the use of bridging hybrid silanes (BTEO,BTEE, and BMDEE) which are known to have increased high pII stability,as well as the use of synthetically relevant groups. For example,particles containing surface vinyl groups can be further reacted by thefollowing transformation (not limited to); oxidation, polymerization,radical addition or metathesis. Particles containing surface thiolgroups can be further reacted by the following transformation (notlimited to); oxidation, radical addition, or disulfide bond formation.Particles containing surface phenyl groups can be further reacted by thefollowing transformation (not limited to); protodesilylation or aromaticsubstitution. As shown in FIG. 1 these nonporous hybrid materials arehighly spherical particles that can have varying particle sizedistribution depending on synthetic conditions. FIG. 1 contains SEMimages of product 1h and 1l. Product 1h clearly has a wider particlesize distribution than product 11. The assessment of particle sizedistribution can also be made by determining the 90/10 ratio. Thisapproach is suitable to prepare products with 90/10 ratios<1.20 and90/10 ratios between 1.20-1.55. Differences in particle sizedistributions impacts packed bed structure and pressure of packed bedsof chromatographic materials.

TABLE 1 Particle Spherical Silanes Size Particles Product (vol/volRatio) % C (μm) (Y/N) 1a PTES 42.4% 1.3 Y 1b BTEO/PTES 29.4% — Y (1:2)1c BTEO/PTES 29.2% — Y (2:1) 1d BTEE/PTES — — Y (1:2) 1e BTEE/PTES — — N(2:1) 1f BMDEE/PTES — — N (2:1) 1g BMDEE/PTES 41.6% 1.3 Y (1:1) 1hBMDEE/PTES 49.8% 1.4 Y (1:5) 1i VTES/PTES 26.0% — Y (10:1) 1j VTES/PTES— — Y (3.3:1) 1k VTES/PTES — — Y (1:1) 1l VTES/PTES 30.6% 1.1 Y (1:2.5)1m VTES/PTES 26.0% 2.3 Y (1:9) 1n VTES 23.7% 1.2 Y 1o MPTMS 25.9%  0.88Y

Example 2

Nonporous hybrid particles were formed following a modification of areported process {U.S. Pat. Nos. 4,983,369 and 4,911,903}. To a cleanNalgene bottle (125 mL) was added a stir bar, water (14 mL), ethanol (80mL), and NH₄OH (7 mL, 14.8 M). One or more alkoxysilanes, includingtetraethoxysilane (TEOS, Gelest, Morrisville, Pa.),phenyltriethoxysilane (PTES, Gelest, Morrisville, Pa.), ormercaptopropyltrimethoxysilane (MPTMS, Lancaster Chemical, Lancaster UK)were added with stirring (600 rpm, 4 mL, 25° C.). The reaction wassealed and the onset of turbidity was monitored. The formation ofspherical particles was further monitored over 24 h by light microscopy.The particles were purified and isolated by repeated centrifugation fromethanol (3×100 mL) and water (3×100 mL). The particles were air driedfor 12 h and then vacuum dried (70° C., 30 mm Hg) for 12 h. Carboncontent was determined by combustion analysis. Average particle size wasdetermined by SEM.

TABLE 2 Silanes Particle Spherical (vol/vol Size Particles ProductRatio) % C (μm) (Y/N) 2a TEOS 3.5 0.55 Y 2b PTES/TEOS 18.4 0.72 Y (1:1)2c MPTMS/TEOS 22.4 0.81 Y (1:1)

Example 3

Product 2c was thermally treated in an air muffled oven at 700° C. for 3h. The resulting nonporous silica product (3a) had no organic content.

Example 4

One or more organoalkoxysilanes (all from Gelest Inc., Morrisville, Pa.or United Chemical Technologies, INC., Bristol, Pa.) were mixed withethanol (anhydrous, J. T. Baker, Phillipsburgh, N.J.) and 0.1 Nhydrochloric acid (Aldrich, Milwaukee, Wis.) in a flask. The resultingsolution was agitated and refluxed for 16 hours in an atmosphere ofargon or nitrogen. Alcohol was removed from the flask by distillation atatmospheric pressure. Residual alcohol and volatile species were removedby heating at 95-120° C. for 1-2 hours in a sweeping stream of argon ornitrogen. The resulting polyorganoalkoxy siloxanes (POS) were clearviscous liquids. The chemical formulas are listed in Table 3 for theorganoalkoxysilanes used to make the product POS. Specific amounts arelisted in Table 4 for the starting materials used to prepare theseproducts.

TABLE 3 Organoalkoxysilane A Organoalkoxysilane or Alkoxysilane B MolarRatio Product Chemical Formula Chemical Formula A:B 4a(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ — 1:0 4b (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃(CH₃CH₂O)₃Si(CH₂)₈Si(OCH₂CH₃)₃ 4:1 4c (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃(CH₃CH₂O)₂(CH₃)Si(CH₂)₂Si(CH₃)(OCH₂CH₃)₂ 1:4

TABLE 4 Organosilane Organosilane 0.1N A B HCl Ethanol Viscosity Product(g) (g) (g) (g) % C (cP) 4a 130 — 11.5 42.2 34.6 227 4b 100 31 11.1 40.636.2 262 4c 27.8 100 8.2 45.2 37.9 45

Example 5

Following a modified process of WO2008103423, An aqueous mixture ofTriton® X-100 (5.6 g, X100, Dow Chemical, Midland, Mich.), deionizedwater and ethanol (52 g, EtOH; anhydrous, J. T. Baker, Phillipsburgh,N.J.) was heated at 55° C. for 0.5 h. In a separate flask, an oil phasesolution was prepared by mixing a POS (58 g) from Example 4 for 0.5hours with toluene (Tol; HPLC grade, J. T. Baker, Phillipsburgh, N.J.).Under rapid agitation, the oil phase solution was added into theEtOH/water/X100 mixture and was emulsified in the aqueous phase using arotor/stator mixer (Model 100L, Charles Ross & Son Co., Hauppauge,N.Y.). Thereafter, 30% ammonium hydroxide (44 mL, NH₄OH; J. T. Baker,Phillipsburgh, N.J.) was added into the emulsion. Suspended in thesolution, the gelled product was transferred to a flask and stirred at55° C. for 16 h. Formed particles were isolated on 0.5 μm filtrationpaper and washed consecutively with copious amounts of water andmethanol (HPLC grade, J. T. Baker, Phillipsburgh, N.J.). The particleswere then dried at 80° C. under vacuum for 16 hours. Specific amounts ofstarting materials used to prepare these products are listed in Table 5.The % C values, specific surface areas (SSA), specific pore volumes(SPV) and average pore diameters (APD) of these materials are listed inTable 5. Materials prepared by this approach are highly spherical by SEM(FIG. 2), and have little to no porosity (SSA≤24 m²/g, SPV≤0.1 cm³/g).Materials prepared by this approach are larger and have broader particlesize distributions than those prepared in Examples 1-3. Modifications inshear rate or addition of charged co-surfactants can be used to increaseor decrease average particle size. Classification techniques can be usedto isolate individual product fractions of desired size range (1-15 μm).This approach is suitable to prepare products with 90/10 ratios<1.20 and90/10 ratios between 1.20-1.55. Differences in particle sizedistributions impacts packed bed structure and pressure of packed bedsof chromatographic materials.

TABLE 5 SSA Toluene Water m²/ SPV dp₅₀ ⁹⁰/₁₀ Product POS (g) (g) % C (g)(cm³/g) (μm) Ratio 5a 4a 5.2 360 30.6 17 0.03 5.8 3.8 5b 4b 10.5 36035.2 5 0.01 13.9 4.6 5c 4c 5.2 280 30.9 24 0.10 14.6 6.5

Example 6

Non-porous particles are prepared by thermal treatment of porous silicaand hybrid inorganic/organic particles in an air muffled oven at1,000-1,200° C. for 20-40 hours. Example of porous hybrid particlesincluded (but are not limited to) examples in Jiang {U.S. Pat. Nos.6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}. Theresulting nonporous silica products have no organic content. Thesematerials maintain the general morphology and particle size distributionof the feed material. Average particle size decreases in this process.The degree of particle size decrease depends on the composition, densityand porosity of the feed material. Any agglomerated materials areremoved through grinding or classification. This approach is suitable toprepare products with 90/10 ratios<1.20 and 90/10 ratios between1.20-1.55. Differences in particle size distributions impacts packed bedstructure and pressure of packed beds of chromatographic materials.

Example 7

Following the reports of Kievsky {IEEE Transactions on Nanotechnology,2005, 4, 5, 490}, rod shaped materials were prepared through thehydrochloric acid catalyzed hydrolysis of tetraethoxysilane (TEOS,Gelest, Morrisville, Pa.) in water in the presence of cetyltrimethylammonium chloride (CTAC, Aldrich, Milwaukee, Wis.). Products werecollected on a filter and were washed with water and methanol. Theproducts were dried under vacuum (80° C., 12 h) and were submitted forSEM characterization. Depending on concentration of water (336 mL),hydrochloric acid (0.8-1.7 mol), CTAC (0.02-0.04 mol) and TEOS (0.02mol), initial agitation, reaction time and temperature (4-25° C.) avariety of different material morphologies were generated, includingstraight rods, bent rods, spirals, and spherical particles. Thisapproach is suitable to prepare products with distributions of lengthsand thicknesses. Isolation of sized samples and removal of anyagglomerated materials is achieved through classification. Differencesrod lengths and thickness are an important variable that impacts packedbed structure and pressure of packed beds, alone or in a mixture withspherical particle packings.

Example 8

Modification of experiment detailed in Example 7 to replacetetraethoxysilane with the use one or more of the following (but notlimited to): phenyltriethoxysilane; phenyltrimethoxysilane;phenylethyltriethoxysilane; phenylethyltrimethoxysilane;ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane;methyltrimethoxysilane diethyldiethoxysilane; diethyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(triethoxysilyl)ethane; 1,2-bis(trimethoxysilyl)ethane;1,2-bis(methyldiethoxysilyl)ethane; 1,2-bis(methyldimethoxysilyl)ethane;vinyltriethoxysilane; vinyltrimethoxysilane;mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane;1,2-bis(triethoxysilyl)ethene; 1,2-bis(trimethoxysilyl)ethene;1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane;1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(triethoxysilylethyl)benzene;1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane;hexyltrimethoxysilane; chloropropyltriethoxysilane;chloropropyltrimethoxysilane; octadecyltrimethoxysilane;octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane;3,3.3-trifluoropropyltrimethoxysilane;3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane;3-cyanobutyltrimethoxysilane; methacryloxypropyltrimethoxysilane;methacryloxypropyltriethoxysilane; acetyloxyethyltrimethoxysilane;acetyloxyethyltriethoxysilane; chloroethyltriethoxysilane;chloroethyltrimethoxysilane; fluorotriethoxysilane; orfluorotrimethoxysilane alone or in a mixture with tetraethoxysilane ortetramethoxysilane. Products were collected on a filter and were washedwith water and methanol. The products are dried under vacuum (80° C., 12h) and are submitted for SEM characterization. Through optimization ofreagents and temperature conditions a variety of different materialmorphologies are generated, including straight rods, bent rods, spirals,and spherical particles. Removal of excess surfactant is achievedthrough extraction. Isolation of sized samples and removal of anyagglomerated materials is achieved through classification. This approachis suitable to prepare products with distributions of lengths andthicknesses. Isolation of sized samples and removal of any agglomeratedmaterials is achieved through classification. Differences rod lengthsand thickness are an important variable that impacts packed bedstructure and pressure of packed beds, alone or in a mixture withspherical particle packings.

Example 9

The porosity of products obtained in Example 7 and 8 are reduced bythermal treatment in an air muffled furnace at 700-1,200° C. for 10-72hours. Isolation of sized samples and removal of any agglomeratedmaterials is achieved through classification.

Example 10

Selected products from Examples 8 and 9, or porous silica (SSA between5-1,000 m²/g; SPV between 0.1-1.6 cm³/g; and APD between 10-1000 Å) andhybrid inorganic/organic particles (SSA between 5-1,000 m²/g; SPVbetween 0.1-1.6 cm³/g; and APD between 10-1000 Å) are partially orcompletely pore filled with a mixture of one or more of the following;polymer, polymerizable monomer, silane, polyorganosiloxanes, ornanoparticles (5-200 nm) of diamonds, aluminum, gold, silver, iron,copper, titanium, niobium, zirconium, cobalt, carbon, silicon, silicacarbide, cerium or any oxides thereof. The use of nanoparticles ofdiamonds allows for improved thermal conductivity of these materials.The use of ferromagnetic and ferrimagnetic nanoparticles, includes (butis not limited to): magnetite (ferrous ferric oxide); maghemite; yttriumiron garnet, cobalt, CrO₂; and ferrites containing iron and Al, Mg, Ni,Zn, Mn or Co). These magnetic materials allow for magnetic capture andprocessing of these materials. Examples of silanes and polyorganosilanesinclude (but are not limited to) those included in Example 4 and Jiang{U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO2008/103423}. Examples of polymers include latexes, epoxides,methacrylates, styrene, divinyl benzene, polysaccharides, dendrigrafts,hyperbranched polymers, and others included in Polymer Handbook {4^(th)edition, J. Brandrup; E. H. Immergut; E. A. Grulke; editors: Wiley:Hoboken, N.J., 1999}. The filling of these porous particles can beperformed by creating a mixture of additives in a solvent including (butnot limited to) methylene chloride, water, acetone or ethanol followedby slow evaporation using an efficient rotary evaporator (0-78° C., 1-24h), to yield a free flowing powder. Alternatively, dry powder can betumbled with additives in a polyethylene bottle at 0-100° C. for 1-24h), to yield a free flowing power. The powder produced can be washedwith a suitable solvent including (but not limited to) ethanol ormethanol.

When silanes or polyorganosiloxanes are employed as additives,hydrolytic condensation can be performed using an aqueous solution ofammonium hydroxide and an alcohol, including (but not limited to)ethanol, isopropanol, or methanol. After stirring for 2-20 hours theproduct is collected on a filter and is washed with water and methanolor acetone. The product is dried under vacuum (80° C., 12 h) and issubmitted for SEM characterization.

When polymerizable monomers are employed as additives, polymerization isperformed using an appropriate initiator including (but not limited to)free radical initiators, ring opening polymerization catalysts,metathesis catalysts, and living polymerization catalysts. Afterstirring for 2-20 hours the product is collected on a filter and iswashed with water and toluene or acetone. The product is dried undervacuum (80° C., 12 h) and is submitted for SEM characterization.

This process is repeated as needed to further reduce porosity andincrease amounts of additives in the pore structure. Interval approachesof silanes or polyorganosiloxanes additives with polymer additives areperformed as needed to further reduce porosity and increase amounts andtypes of additives in the pore structure. Layered or repeatingstructures of additives can be prepared by this approach. For example, acomposite material containing both diamonds and magnetite would bebeneficial for thermal conductivity improvements and magnetic captureprocessing. A material that contains alumina or titania is suitable forglycopeptides, phosphopeptide and phospholipids separations. A materialthat contains ceria may be suitable for phospholipid andphosphatidylcholines separations.

Materials prepared by this approach are free flowing and maintain thegeneral morphology and particle size distribution of the porous feedmaterial. This approach is suitable to prepare products with 90/10ratios<1.20 and 90/10 ratios between 1.20-1.55. SPV decreases in thisprocess. Exemplary products of this process are nonporous. The degree ofporosity reduction depends on the amount of additives incorporated inthe pore structure. Any agglomerated materials can be removed throughgrinding or classification.

Example 11

Composite materials of Example 10 are thermally treated at 700-1,200° C.for 10-40 hours to further reduce SPV. This thermal treatment isperformed in air, under an inert atmosphere, or in a reducing atmospheredepending on compatibility of the additives employed. Materialscontaining diamond or magnetite employ an inert or reducing atmosphereis used to prevent oxidation.

Materials prepared by this approach are free flowing and maintain thegeneral morphology and particle size distribution of the porous feedmaterial. SPV decreases in this process. Exemplary products of thisprocess are nonporous. The degree of porosity reduction depends on thecomposition, density and porosity of the feed material. Any agglomeratedmaterials can be removed through grinding or classification.

Example 12

Following the report of Zhang {Functional Materials Letters, 2010, 3, 2,125.} spheroidal magnetite particles were prepared through thesolvothermal reaction of iron trichloride. In a 600 mL stainless steelautoclave equipped with a removable glass liner and an overhead mixer amixture of anhydrous iron (III) chloride (Fisher Scientific), deionizedwater, ethylene glycol (Sigma-Aldrich, St. Louis, Mo.), polyethyleneglycol (PEG 3400, Sigma-Aldrich, St. Louis, Mo.) and urea(Sigma-Aldrich, St. Louis, Mo.) were stirred at 50° C. until completelydissolved. The headspace was evacuated under vacuum and the pressurereactor was sealed before being heated (with or without stirring) to220° C. and was held at this temperature overnight. The reactor wascooled to ambient temperature. Products were isolated in a magneticseparator, and were washed by repeated resuspension in deionized water.Specific reaction data is provided on Table 6. Percent conversion ofiron trichloride to magnetite was determined by iron concentrationsanalysis by digestion in hydrochloric acid and complexation withpotassium thiocyanate. Magnetic properties were determined by VSM. Phaseconfirmation was determined by XRD. Particle size and standard deviationwere determined by measuring individual particles by SEM (minimumparticles counted >60). The effects of temperature, solvent, cosolvent,reagent concentrations, and stirring speed were investigated as part ofthe process optimization. Specific product data are listed in Table 6.As shown in FIG. 3, products obtained by this approach are spheroidal. Alow level of agglomerated materials can be observed in this figure,which can be reduced through optimization and control of reactionconditions. Products 12j-121m showed the impact of increased stirringrate on this reaction. As stirring rates increase the average particlesize decreases, and the particle size standard deviation decreases. XRDanalysis of product 12j indicates 100% magnetite with an average domainsize of 64.6 nm.

TABLE 6 ethylene PEG Particle Standard FeCl₃ Water glycol 3400 ureaStirring Size Deviation % Product (g) (mL) (g) (g) (g) RPM (nm) (nm)Conversion 12a 2.5 1.62 133.7 5.0 4.5 0 217 23 45 12b 2.5 1.62 134.5 5.14.5 0 216 26 44 12c 7.3 0.00 404.2 14.6 13.0 0 68 40 45 12d 7.3 4.75403.0 14.6 13.1 0 269 39 33 12e 7.5 9.7 401.3 14.6 13.1 0 449 97 71 12f7.4 19.5 405.1 14.2 13.1 0 158 41 72 12g 7.3 4.75 407.1 14.6 13.1 0 40563 47 12h 5.1 3.24 134.5 5.0 4.5 0 68 12 44 12i 14.6 9.46 403.0 14.613.1 0 103 21 47 12j 103.9 140.0 5574.4 200.3 180.0 0 496 109 75 12k103.4 139.8 5572.3 200.0 179.9 34 207 21 78 12l 103.5 140 5570.0 200.0180.0 96 137 15 82 12m 103.7 140.0 5570.2 198.3 179.7 250 55 12 69

Example 13

Magnetite core particles (0.1-0.5 μm) from Example 12 are reacted withtetraethoxysilane in an aqueous ammonical ethanol solution following ageneral process described by Example 2, U.S. Pat. Nos. 4,983,369,4,911,903, Giesche {J. Eur. Ceram. Soc., 1994, 14, 189; J. Eur. Ceram.Soc., 1994, 14, 205} or Nozawa {Phys. Rev. E: Stat., Nonlinear, SoftMatter Phys., 2005, 72 (1), 011404}. The product of this is a freeflowing powder with a thick silica shell material. The final particlesizes for these materials are controlled between 0.8-1.7 μm throughchanges in reaction conditions. Products are isolated by centrifugation,magnetic capture or filtration, and are washed with copious amounts ofwater and methanol. The product is air dried before drying under vacuum(80° C., 12 h) and is submitted for SEM characterization. Anyagglomerated materials can be removed through grinding orclassification. Products prepared by this approach have little to noporosity. This silica layer on magnetite is advantageous because itreduces iron dissolution and reduces undesired secondary interactionsbetween analytes and the magnetite surface during a chromatographicseparation.

Example 14

The process described in Example 13 is applied to other materials,including ones prepared in Examples 1-3, 5-11 as well as diamond,aluminum, gold, silver, iron, copper, titanium, niobium, zirconium,cobalt, carbon, silicon, silica carbide, cerium or any oxides thereof.The size of these materials is between 0.01-2.0 μm. These materials canexist as dispersed particles or aggregates of nanoparticles. The silicalayer thickness is controlled in this process through changes inreaction conditions and can produce final product sizes between 0.8-5μm. Any agglomerated materials can be removed through grinding orclassification. Products prepared by this approach are free flowing andhave little to no porosity. While this approach is applicable to avariety of different feed morphologies, a significant degree of roundingoccurs during this process. This rounding increases with silica layerthickness, and can decrease the observation of flat surfaces or sharpedges on these materials. This is advantageous for use as liquidchromatographic packing since sharp edges can lead to increase materialfracturing and fines generation during packing of the chromatographicdevice.

Example 15

The process described in Example 13 is applied to other materials havingnon-spherical morphologies, including (but not limited to) spirals,capsules rings, discoidal, concave disks, spools, rings, helix, saddles,cross, cube, derby, helix, cylinders, and tubes. Examples of dumbbell,doughnut, rod, spiral, and gyroid shaped materials have been reported{Doshi, N. PNAS, 2009, 106, 51, 21495; Alexander, L. Chem. Commun.,2008, 3507; Naik, S. J. Phys. Chem. C 2007, 111, 11168; Pang, X.Microporous and Mesoporous Materials 2005, 85, 1; Kievsky, Y. IEEETransactions on Nanotechnology, 2005, 4, 5, 490; Sugimoto, T. inMonodispersed Particles, (Elsevier Science BV, Amsterdam) 2001; Ozin, G.Adv. Mater., 1997, 9, 662}. Examples of ferrimagnetic and ferromagneticiron oxide rings and capsules have been reported {Wu, W. J. Phys. Chem.C 2010, 114, 16092; Jia, C.-J. J. Am. Chem. Soc. 2008, 130, 16968}. Theexternal diameter of these feed materials is between 0.2-5 μm. Thesilica layer thickness is controlled in this process through changes inreaction conditions and produces final external sizes between 0.3-5.5μm. Any agglomerated materials can be removed through grinding orclassification.

Example 16

The process described in Example 13-15 is modified to replacetetraethoxysilane with one or more of the following (but not limitedto): phenyltriethoxysilane; phenyltrimethoxysilane;phenylethyltriethoxysilane; phenylethyltrimethoxysilane;ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane;methyltrimethoxysilane diethyldiethoxysilane; diethyldimethoxysilane1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene;1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene;1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane;1,2-bis(trimethoxysilyl)ethane; 1,2-bis(methyldiethoxysilyl)ethane;1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane;vinyltrimethoxysilane; mercaptopropyltrimethoxysilane;mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethene;1,2-bis(trimethoxysilyl)ethene; 1,1-bis(triethoxysilyl)ethane;1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene;1,4-bis(trimethoxysilylethyl)benzene;1,3-bis(triethoxysilylethyl)benzene;1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxysilane;hexyltrimethoxysilane; chloropropyltriethoxysilane;chloropropyltrimethoxysilane; octadecyltrimethoxysilane;octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane;3,3.3-trifluoropropyltrimethoxysilane;3,3.3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; and3-cyanobutyltrimethoxysilane alone or in a mixture withtetraethoxysilane or tetramethoxysilane.

The silica shell thickness is controlled in this process through changesin reaction conditions and can produce final product sizes between0.8-1.7 μm. Any agglomerated materials can be removed through grindingor classification. Products prepared by this approach are free flowingand have little to no porosity.

Example 17

Selected products in Example 13-16 are thermally treated at 700-1,200°C. for 10-72 hours to further reduce SPV. This thermal treatment isperformed in air, under an inert atmosphere, or in a reducing atmospheredepending on the additives employed. When additives of diamond ormagnetite are used, an inert or reducing atmosphere is used to preventoxidation.

Materials prepared by this approach are free flowing and maintain thegeneral morphology and size distribution of the porous feed material.SPV decreases in this process. Exemplary products of this process arenonporous. The degree of porosity reduction depends on the composition,density and porosity of the feed material. Any agglomerated materialscan be removed through grinding or classification.

Example 18

Product 12j (0.2 g, 496 nm) from Examples 11 was twice washed withdeionized water (500 mL) followed by twice washing with an aqueoussolution of 0.7% poly(vinylpyrrolidone) (PVP, MW=360,000, 400 mL,Aldrich). Materials were isolated in a magnetic separator. The materialwas then dispersed in an aqueous solution of 0.7% PVP (400 mL) usingsonication (10 minutes), followed by gentile agitation for 16 hours. Thematerial was then allowed to completely settle and the volume wasreduced by 28 mL. The mixture was then transferred to a round bottomflask equipped with overhead stirring and a condenser. To this mixturewas added anhydrous ethanol (200 mL, JT Baker) and 28% (w/v) ammoniumhydroxide (28 mL, Fisher Scientific). This mixture was stirred atambient temperature for 20 minutes.

In a separate flask a solution of distilled tetraethoxysilane (0.388 mL,TEOS, Gelest) was diluted in anhydrous ethanol (4.00 mL). This solutionwas then added to the particle mixture in four equal aliquots spaced 20minutes apart, with continued stirring. The reaction was then allowed tocontinue for an additional 60 minutes. Materials were isolated in amagnetic separator and were washed twice with anhydrous ethanol andtwice with deionized water.

This material was resuspended in 0.7% PVP (400 mL) and the growthprocess described above was repeated until the final particle size wasachieved. The product (18a) was isolated in a magnetic separator and waswashed twice with anhydrous ethanol and five times in deionized water. Asample of this product was submitted for SEM analysis. Particle size andstandard deviation was determined by measuring individual particles bySEM (minimum particles counted ≥60). The final product indicated a finalparticle size of 1.198±0.119 μm.

Example 19

The alkoxysilanes used in Example 1 are modified to include substitutedbenzenes, including (but not limited to) 1,4-bis(triethoxysilyl)benzene,1,4-bis(trimethoxysilyl)benzene, 1,3-bis(tricthoxysilyl)benzene,1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene,1,3,5-tris(trimethoxysilyl)benzene, andbis(4-triethoxysilylphenyl)diethoxysilane. Bridging arylene materialshave been shown to have improved thermal stability over traditionalhybrid inorganic/organic materials {Shea, K. J. Non-Cryst. Solids, 1993,160, 234}. Particles prepared by this approach are spherical and freeflowing.

Example 20

The alkoxysilanes used in Example 2 are modified to include substitutedbenzenes, including (but not limited to) 1,4-bis(triethoxysilyl)benzene,1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene,1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene,1,3,5-tris(trimethoxysilyl)benzene, andbis(4-triethoxysilylphenyl)diethoxysilane. Materials prepared by thisapproach are free flowing and have improved thermal stability overtraditional hybrid inorganic/organic materials.

Example 21

Superficially porous silica layers are formed on selected hybrid corematerials from Example 1, 2, 19 and 20 using a modified processdescribed by Kirkland {US 20070189944; 20080277346}. In this approach0.8-1.7 μm hybrid core materials are treated with a 0.1-0.5 wt %solution of one or more polyelectrolytes including (but not limited to):poly(diallyldimethylammonium chloride, polyethylenimine andpoly(allylamine hydrochloride) in water. The molecular weight of thesepolyelectrolytes can vary between 2,000 and 500,000. These materials arewashed with water using repeated centrifugation, before redispersing inwater. A 2-10 wt % solution of silica sols (8-85 nm) is then added withmixing. These materials are washed with water using repeatedcentrifugation. This process of polyelectrolyte treatment followed bywashing, silica sol treatment, and washing can be repeated until a finalparticle size is achieved. Final drying of product is performed in avacuum oven or lyophilizer at ambient to elevated temperatures.

Products prepared in this manner have both silica sols andpolyelectrolyte on the core material. In order to remove thepolyelectrolyte thermal treatment at temperatures greater than 500° C.(10-20 hours) is employed. To further strengthen these materials, asecond thermal treatment at 825-1000° C. for 10-20 hours is employed.These thermal treatments are performed in air, under an inertatmosphere, or in a reducing atmosphere depending on the additivesemployed. When additives of diamond or magnetite are used, an inert orreducing atmosphere is used to prevent oxidation.

While materials prepared by this process are free flowing sphericalsuperficially porous materials with rough surface features, the thermaltreatments steps remove all carbon content from these materials.Expected improvement in chemical stability of a hybrid core inchromatographic applications is not realized by this approach. Similarperformance with commercially available silica superficially porousmaterials is achieved by this approach.

Example 22

The polyelectrolyte of Example 21 is modified to include the use ofchemically degradable polymers, including (but not limited to)polyethylene glycol, polypropylene glycol, polymethacrylate,polymethylmethacrylate, poly(acrylic acid), and polylactic acid basedpolymers containing pendant primary, secondary, or tertiary aminogroups. For example, polyethylene glycol (PEG) based polyether aminesare described in U.S. 7,101,52, and others are commercially available asJeffamine polyetheramines (Huntsman Corporation).

Products prepared in this manner have both silica sols and polymer onthe core material. In order to remove the polymer, different approachesare employed that do not require thermal treatment at or above 500° C.Polymethylmethacrylate networks can be decomposed using (3-rayirradiation. Acrylate and methacrylate polymer backbones havingthermally cleavable tertiary ester linkages can decompose between180-200° C. {Ogino, K. Chem. Mater, 1998, 10, 3833}. Polyethylene glycolgroups can be removed by oxidative degradation {Andreozzi, R. WaterResearch, 1996, 30, 12, 2955; Suzuki, J. J. Applied Polymer Science,1976, 20, 1, 93} and microwave assisted template removal using nitricacid and hydrogen peroxide {Tian, B. Chem. Commun., 2002, 1186}. Alisting of other degradable polymer backbones and degradation mechanismis reported in Degradable Polymers: Principles and Applications {EditorsG. Scott and D. Gilead, D., Chapman & Hall (Kluwer) 1995}.

Materials prepared by this process are free flowing sphericalsuperficially porous particles with rough surface features, Expectedimprovements in chemical stability of a hybrid core in chromatographicapplications are realized by this approach. Improvements in chemicalstability of these superficially porous particles over commerciallyavailable silica superficially porous particles are achieved by thisapproach.

After polymer degradation, there is a substantial reduction of polymercontaining primary, secondary or tertiary amino groups remain withinthese superficially porous materials. Further processing steps can beperformed to further reduce and remove this polymer content. Anyagglomerated materials or fine materials can be removed throughclassification.

These particles still contain carbon content of the core hybridparticles. To improve pore diameter and further strengthen thesesuperficially porous materials, hydrothermal treatment method of Jiang{U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO2008/103423} are employed. Alternatively a surrounding material methoddescribed by Wyndham {WO 2010/141426} can be used to strengthen thesesuperficially porous materials. The addition of a surrounding materialdecreases the porosity of these materials. The surrounding materialmethod is of particular importance when a hybrid inorganic/organicsurrounding material is used on the silica-sol superficially porouslayer. Such materials have improved chemical stability over commerciallyavailable silica superficially porous particles. When the surroundingmaterial contains nanoparticles, including (but not limited to)nanodiamonds—as noted in Examples 12 and 13 of Wyndham {WO2010/141426}—improvements in thermal conductivity can be achieved.

Example 23

The core material of Example 21 is modified to include the precursor orproduct materials from Examples 5-18. Included in this are spherical,irregular, rod-shaped and toroid-shaped materials. Included in this are0.5-1.5 μm cores that are diamond, magnetite, coated diamond, or coatedmagnetite.

Example 24

The core material of Example 22 is modified to include the precursor orproduct materials from Examples 5-18. Included in this are spherical,irregular, rod-shaped and toroid-shaped materials. Included in this are0.5-1.9 μm cores that are diamond, magnetite, coated diamond, or coatedmagnetite.

Example 25

The silica sol used in Examples 21-24 is modified to include the use ofhybrid sols. Hybrid sols are prepared by the condensation of hybridinorganic/organic alkoxysilanes in the presence or absence of atetraethoxysilane or tetramethoxysilane. Similar sol sizes can beachieved in this approach (8-85 nm) by this approach. Alternatively ahybrid layer can be formed by surface modifying preformed silica sols(8-85 nm). The use of a hybrid core material and chemically degradablepolymers containing pendant primary, secondary, or tertiary amino groupsdescribed in Example 22, allows for the formation of hybridsuperficially porous materials. Alternatively 0.8-1.9 μm nonporoussilica cores are used. These materials contain carbon content of thecore and porous layers. To improve pore diameter and further strengthenthese superficially porous materials, hydrothermal treatment method ofJiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO2008/103423} are employed. Alternatively a surrounding material methoddescribed by Wyndham {WO 2010/141426} can be used to strengthen thesesuperficially porous materials. No high temperature thermal treatment(>600° C.) is used in this approach.

Example 26

The process of Examples 21-25 is modified to replace a part of all ofsols used with similar size sols, including (but not limited to)diamonds, aluminum, gold, silver, iron, copper, titanium, niobium,zirconium, cobalt, carbon, silicon, silica carbide, cerium or any oxidesthereof.

Example 27

The process of Examples 21-26 is modified to include incorporation ofone or more nanoparticles within the superficially porous layer,including (but not limited to) nanoparticles listed in Example 10.

Example 28

Nonporous silica particles (1.26 μm, 10.4 g), that were previouslythermally treated at 600° C. (10 h) and dehydroxylated using 10% nitricacid (Fisher scientific) were dispersed in 80 mL of solvent(water:anhydrous ethanol 2:1 v/v) by sonication for 10 minutes.Separately, octadecyltrimethylammonium bromide (0.43 g, C₁₈TAB,Sigma-Aldrich) was dissolved in 80 mL of solvent (water:anhydrousethanol 2:1 v/v). The C₁₈TAB solution was then added into the particlesolution and was sonicated for 10 minutes. This solution was labeledsolution A. In a separate beaker of pluronic P123 (8.44 g,Sigma-Aldrich) was dissolved in 240 mL of solvent (water:anhydrousethanol 2:1 v/v) and was labeled solution B. Solution B (240 mL) wasadded into solution A (160 mL) and was sonicated for 20 minutes. Themixture was then transferred into a 1 L round bottom flask and stirredat 600 rpm. Ammonium hydroxide solution (30%, 12 mL, J. T. Baker) wasadded into the flask and allowed to continue stirring for 5 minutes.1,2-bis(triethoxysilyl)ethane (2.3 mL, BTEE, Gelest) was then added overa minute. The reaction was allowed to continue with stirring for anhour. The final concentrations reagents used were C₁₈TAB (2.6-10.5 mM),Pluronic P123 (3.5-13.8 mM), and BTEE (0.015-0.030 M).

During the washing step, the sample was diluted four times the samplevolume with deionized water followed by centrifugation (Forma ScientificModel 5681, 2,500 rpm, 6 min). The wash sequence was repeated two timesusing sonication to redisperse particles.

The growth process was repeated three times to yield four hybrid layerson the nonporous silica core. With each layer the volume of solution A(5-7 vol %), solution B (6 vol %) and ammonium hydroxide (3-10 vol %)were increased to compensate for the increase in solids volume aftereach growth layer while maintaining the concentration of the reagentsconstant. Amounts of C₁₈TAB, BTEE and ethanol/water used are shown onTable 7. Products were isolated by centrifugation and washedconsecutively with copious amounts of water and methanol (HPLC grade, J.T. Baker, Phillipsburgh, N.J.). The particles were then air dried andvacuum dried at 80° C. under vacuum for 16 hours. Products weresubmitted for SEM analysis.

Reactions in this process used <3 mM C₁₈TAB. Very little hybrid layergrowth was observed in this approach. In contrast increased aggregationand elevated amount fine particle (<1 μm) were observed.

TABLE 7 Concentration Ratio Concentration C₁₈TAB ETOH:H₂O BTEE SEMProduct (mM) (v/v) (M) Comments 28a 2.6 1:2 0.03 Small bumps on theparticle surface Particle were aggregated 28b 2.6 1:2 0.02 Welldispersed particles Particles did not appear to grow after the secondgrowth 28c 2.6 1:2 0.03 Small bumps on particle surface 28d 2.6 1:2 0.02Particles were aggregated No fine particles observed 28e 2.6 1:2 0.03Small bumps on the particle surface 28f 2.6 1:1 0.02 Particles did notappear to grow after the second growth Well dispersed particles No fineparticles observed

Example 29

Nonporous silica particles (10.4 g, 1.26 Mm), that were previouslythermally treated at 600° C. (10 h) and dehydroxylated using 10% nitricacid (Fisher scientific), were dispersed in 100 mL of solvent(water:anhydrous ethanol 2:1 v/v) by sonicating for 10 minutes.Separately, octadecyltrimethylammonium bromide (2.46 g, C₁₈TAB,Sigma-Aldrich) was dissolved in 100 mL of solvent (water:anhydrousethanol 2:1 v/v). The C₁₈TAB solution was then added into the particlesolution and was sonicated for 10 minutes. This solution was labeledsolution A. In a separate beaker of Pluronic P123 (39.0 g,Sigma-Aldrich) was dissolved in 400 mL of solvent (water:anhydrousethanol 2:1 v/v) and was labeled solution B. Solution B (400 mL) wasadded into solution A (200 mL) and allowed to continue sonicate for 20minutes. The mixture was then transferred into a 1 L round bottom flaskand stirred at 750 rpm. Ammonium hydroxide solution (30%, 24 mL, J. T.Baker) was added into the flask and allowed to continue stirring for 5minutes. 1,2-bis(tricthoxysilyl)ethane (6 mL, BTEE, Gelest) was firstdiluted with anhydrous ethanol (dilution factor=3) and then added to theflask with a peristaltic pump (ISMATEC, ISM596D equipped with 1/32 inchdiameter PTFE tubing from Cole-Palmer) at a constant flow rate (50ML/min). The reaction was allowed to continue stirring until all BTEEwas added, allowed to stir for an extra hour before washing. The finalconcentrations reagents used were C₁₈TAB (2.6-17.27 mM), Pluronic P123(3.5-22.16 mM), and BTEE (0.020-0.030 M).

The wash steps were performed as detailed in Example 28. The growthprocess was done once to grow a hybrid layer on the nonporous silicacore. Reaction details are included on Table 8. Products were isolatedby centrifugation and washed consecutively with copious amounts of waterand methanol (HPLC grade, J. T. Baker, Phillipsburgh, N.J.). Theparticles were then air dried and at 80° C. under vacuum for 16 hours.Products were submitted for SEM analysis. Particle size was determinedby measuring individual particles by SEM. As shown in Table 8, andincrease in C₁₈TAB concentration (2.6-13.6 mM) results in an increase inshell thickness (0.04-0.16 Mm) by this approach. Similar to Example 28,reactions using less than 3 mM C₁₈TAB had increased aggregation andelevated amount fine particle (<1 μm) were observed. Concentrations ofC₁₈TAB between 8-17 mM advantageously resulted in well formed products.

TABLE 8 Concen- Concen- Product tration tration Particle Shell C₁₈TABBTEE Size Thickness SEM Product (mM) (M) (μm) (μm) Comments 29a 2.6 0.021.33 0.04 Particle with a smooth surface Very little growth Particlesstuck together 29b 5.30 0.03 1.45 0.10 Well dispersed particles No fineparticles observed Smooth particle surface 29c 17.27 0.03 1.57 0.16 Welldispersed particles No fine particles observed Smooth particle surface29d 10.50 0.02 1.55 0.15 Well dispersed particles No fine particlesobserved Smooth particle surface 29e 13.63 0.02 1.51 0.13 Well dispersedparticles No fine particles observed Smooth particle surface

Example 30

An initial hybrid growth layer is formed on rehydroxylated nonporoussilica particles (0.8-1.7 μm, 10.4 g) using a modified process forProduct 29b. These core particles can have 90/10 ratios<1.20 or 90/10ratios between 1.2-1.55. In this reaction 1,2-bis(triethoxysilyl)ethane(6 mL, BTEE, Gelest) is first diluted with anhydrous ethanol (dilutionfactor=3) and is added to the flask with a peristaltic pump (ISMATEC,ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer)at 5-100 μL/min. The particle size is monitored during this growthprocess. The reaction is allowed to continue stirring until the targetparticle size is reached or all BTEE is added. The mixture is allowed tostir for an extra hour before the wash steps, which are performed asdetailed in Example 28.

This process is repeated for products requiring one or more additionalhybrid growth layers. Increases in C₁₈TAB, Pluronic P123, ethanol, andammonium hydroxide are made to maintain a low concentration of solids.C₁₈-TAB concentration is maintained between 8-11 mM, and the mol ratioof C₁₈-TAB/Pluronic P123 was maintained at 1.3:1. Optimizationexperiments showed that lower ratios of these two surfactants leads toincreased aggregation. BTEE is diluted with anhydrous ethanol (dilutionfactor ≥3) and is added to the reaction at a flow rate of 5-100 μL/min.The particle size of these materials is monitored during this growthprocess. The reaction is allowed to continue stirring until the targetparticle size is reached or all BTEE is added. The mixture is allowed tostir for an extra hour before the wash steps, which are performed asdetailed in Example 28.

Products are isolated by centrifugation and are washed consecutivelywith copious amounts of water and methanol (HPLC grade, J. T. Baker,Phillipsburgh, N.J.). The products are then air dried and at 80° C.under vacuum for 16 hours. Products are submitted for SEM, and FIB/SEManalysis. Particle size is determined by measuring individual particlesby SEM. As listed in Table 9, final products have an average particlesize of 1.2-2.7 μm, with shell thickness varying from 0.03-0.60 μm.Products prepared by this approach are free flowing, spherical and havea smooth surface. Products 30a, 30b, and 30g are prepared in one layer.Products 30c-f, 30-h-l are prepared in two to four growth layers.Products 30m-p are prepared in 5-15 layers. This approach allows forsuperficially porous materials with different physical properties to beprepared. For example Products 30d and 30g (1.30 μm); Products 30e and30 h (1.50 μm); Products 30f, 30i and 30 k (1.70 μm); and Products 30mand 30n (2.30 μm) have similar final particle size, but vary in shellthickness and the ratio of shell thickness to radius of the core. Theratio of shell thickness to core radius can be modified over a largerange by this approach (0.04-0.71).

TABLE 9 Initial Core Product Particle Shell Ratio Shell Size SizeThickness Thickness to Product (μm) (μm) (μm) Radius Core 30a 0.80 1.000.10 0.25 30b 0.80 1.10 0.15 0.38 30c 0.80 1.20 0.20 0.50 30d 1.00 1.300.15 0.30 30e 1.00 1.50 0.25 0.50 30f 1.00 1.70 0.35 0.70 30g 1.25 1.300.03 0.04 30h 1.25 1.50 0.13 0.20 30i 1.25 1.70 0.23 0.36 30j 1.25 1.900.33 0.52 30k 1.50 1.70 0.10 0.13 30l 1.50 2.00 0.25 0.33 30m 1.50 2.300.40 0.53 30n 1.70 2.30 0.30 0.35 30o 1.70 2.60 0.45 0.53 30p 1.70 2.900.60 0.71

Example 31

The process of Examples 30 is modified to have a superficially porouslayer formed in a single continued growth layer using rehydroxylatednonporous silica particles (0.8-2.5 μm). These core particles can have90/10 ratios<1.20 or 90/10 ratios between 1.2-1.55. In this reaction1,2-bis(triethoxysilyl)ethane (BTEE, Gelest), diluted with anhydrousethanol (dilution factor=3), is added with a peristaltic pump (ISMATEC,ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer)at 5-100 μL/min. A second solution containing octadecyltrimethylammoniumbromide (C₁₈TAB, Sigma-Aldrich), water, ethanol, Pluronic P123(Sigma-Aldrich) and ammonium hydroxide solution (30%, 24 mL, J. T.Baker) is added using a separate peristaltic pump at a constant rate inorder to maintain concentrations of C₁₈TAB, water, ethanol, PluronicP123, ammonium hydroxide within a range between the rate required tomaintain a uniform ratio of particle surface area (m²) to reactionvolume, to the rate required to maintain a uniform ratio of particlevolume (m³) to reaction volume. The particle size of these materials ismonitored during this growth process. The reaction is allowed tocontinue stirring until the target particle size is reached or all BTEEis added. The mixture is allowed to stir for an extra hour before thewash steps, which are performed as detailed in Example 28.

Final products have an average particle size of 1.0-2.9 μm, with shellthickness varying from 0.03-0.60 μm. Products are submitted for SEM, andFIB/SEM analysis. Particle size is determined by measuring individualparticles by SEM. Products prepared by this approach are free flowing,spherical and have a smooth surface. Analysis of particle by FIB/SEMshows evidence of a single step process, having no observable interlayercontrast.

Example 32

1.26 μm nonporous silica particles (10.4 g) that were previouslythermally treated at 600° C. (10 h) and rehydroxylated using 10% nitricacid (Fisher scientific) were used in this process.

A silica layer was formed by the following process. Particles weredispersed in 80 mL of solvent (water:anhydrous ethanol 2:1 v/v) bysonicating for 10 minutes. Separately, octadecyltrimethylammoniumbromide (0.46 g, C₁₈TAB, Sigma-Aldrich) was dissolved in 80 mL ofsolvent (water:anhydrous ethanol 2:1 v/v). The C₁₈TAB solution was addedinto the particle solution and the mixture was sonicated for 10 minutes.This solution was labeled solution A. In a separate beaker of PluronicP123 (8.44 g, Sigma-Aldrich) was dissolved in 240 mL of solvent(water:anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B(240 mL) was added into solution A (160 mL) and was sonicated for 20minutes. The mixture was then transferred into a 1 L round bottom flaskand stirred at 750 rpm. Ammonium hydroxide solution (30%, 12 mL, J. T.Baker) was added into the flask and allowed to continue stirring for 5minutes. Tetraethoxysilane (4.6 mL, TEOS, Sigma-Aldrich) was added intwo steps. First 2.3 mL of TEOS was added and the reaction was continuedfor 30 minutes before an additional 2.3 mil, of TEOS was added and thereaction allowed continuing for an hour. The wash steps were performedas detailed in Example 28.

A hybrid layer was formed on these particles using the followingprocess. Particles were redispersed in 100 mL solvent (water:anhydrousethanol 2:1 v/v) by sonication. Separately, octadecyltrimethylammoniumbromide (3.0 g, C₁₈TAB, Sigma-Aldrich) was dissolved in 100 mL ofsolvent (water:anhydrous ethanol 2:1 v/v). The C₁₈TAB solution was thenadded into the particle solution and was sonicated for 10 minutes. Thissolution was labeled solution A. In a separate beaker of Pluronic P123(58 g, Sigma-Aldrich) was dissolved in 400 mL of solvent(water:anhydrous ethanol 2:1 v/v) and was labeled solution B. Solution B(400 mL) was added into solution A (200 mL) and allowed to continue tosonicate for 20 minutes. The mixture was then transferred into a 1 Lround bottom flask and was stirred at 750 rpm. Ammonium hydroxidesolution (30%, 24 mL, J. T. Baker) was added into the flask and wasstirred for 5 minutes. In this growth step 1,2-bis(triethoxysilyl)ethane(6 mL, BTEE, Gelest) was first diluted with anhydrous ethanol (dilutionfactor=3) and was added to the flask with a peristaltic pump (ISMATEC,ISM596D equipped with 1/32 inch diameter PTFE tubing from Cole-Palmer)at 50 μL/min. Once all the BTEE was added the reaction was allowed tocontinue for an hour. The product was isolated and was washed asdetailed in Example 28.

A silica layer was then grown on the hybrid layer using the silica layerprocess described above, but the volume of the solution was increased tocompensate for the increase in solids volume while maintaining aconstant concentration of the reagents. A hybrid layer was formed onthis silica layer using the hybrid layer process described above, butthe volume of the solution was increased to compensate for the increasein solids volume while maintaining a constant concentration of thereagents.

Reaction details are included on Table 10. Products were isolated bycentrifugation and washed consecutively with copious amounts of waterand methanol (HPLC grade, J. T. Baker, Phillipsburgh, N.J.). Theparticles were then air dried and at 80° C. under vacuum for 16 hours.Products were submitted for SEM analysis. Particle size was determinedby measuring individual particles by SEM. The advantageous use ofincreased amounts of C₁₈TAB and Pluronic P123 for acceptable hybridlayer growth (32L2 and 32L4) is evident in this data. When C₁₈TABconcentrations were <5 mM, little to no hybrid layer growth is observed.

This process was repeated separately to prepare two additional products.The first (product 32a) had a silica followed by hybrid layer. Thesecond (product 32b) had a silica followed by two consecutive hybridlayers, resulting in an increased hybrid content near the exteriorsurface.

TABLE 10 particle Layer TEOS BTEE C₁₈TAB Sol. P123 Sol. B NH₄OH sizeProduct Type (mL) (mL) (g) (mL) (g) (mL) (mL) (μm) 32L1 Silica 4.6 — 0.5160 8.4 240 15 1.32 32L2 Hybrid — 6.0 3.0 200 58 400 24 1.54 32L3 Silica4.6 — 0.6 200 11 400 15 1.64 32L4 Hybrid — 8.1 5.0 400 92 600 30 1.76

Example 33

The process of Example 28-32 is modified to use tetraethoxysilane in thefirst layer followed by 1,2-bis(triethoxysilyl)ethane or a mixture oftetraethoxysilane and 1,2-bis(triethoxysilyl)ethane in the followinglayer. This solution varies from 0-99 vol % tetraethoxysilane. Thissequence is repeated (2-15 times) to create a distinct silica and hybridlayers. By changing reaction conditions the thickness of the silicaporous layer and the hybrid porous layers can be modified between10-1000 nm. The composition of this 1,2-bis(triethoxysilyl)ethane andtetraethoxysilane mixture can vary for each layer, creating an enrichedhybrid content at the external porous surface. Alternatively thecomposition of this 1,2-bis(triethoxysilyl)ethane and tetraethoxysilanemixture can vary for each layer, creating enriched silica content at theexternal porous surface. For the general process of Examples 29-31, thecomposition of a mixed tetraethoxysilane and1,2-bis(triethoxysilyl)ethane solution can be modified by changing thefeed alkoxysilane solution over the course of these reactions.

Example 34

The process of Example 28-32 is modified to use1,2-bis(triethoxysilyl)ethane in the first layer followed by1,2-bis(triethoxysilyl)ethane or a mixture of tetraethoxysilane and1,2-bis(triethoxysilyl)ethane in the following layer. This solutionvaries from 1-100 vol % tetraethoxysilane. This sequence is repeated(2-15 times) to create a distinct hybrid and silica layers. By changingreaction conditions the thickness of the hybrid porous layers can bemodified between 10-1000 nm. The composition of this1,2-bis(triethoxysilyl)ethane and tetraethoxysilane mixture can vary foreach layer, creating an enriched hybrid content at the external poroussurface. Alternatively the composition of this1,2-bis(tricthoxysilyl)ethane and tetraethoxysilane mixture can vary foreach layer, creating enriched silica content at the external poroussurface. For the general process of Examples 29-31, the composition of amixed tetraethoxysilane and 1,2-bis(triethoxysilyl)ethane solution canbe modified by changing the feed alkoxysilane solution over the courseof these reactions.

Example 35

The core material of Example 28-34 is modified to include the precursoror product materials from Examples 1-3, or 5-20. Included in this arespherical, irregular, rod-shaped and toroid-shaped materials. Includedin this are 0.5-1.9 μm cores that are hybrid, diamond, magnetite, coateddiamond, or coated magnetite.

Example 36

The process of Examples 28-35 is modified to replace a part of all ofthe alkoxysilane used with one or more of the following silanes (but notlimited to) listed in Example 16 and 19, Jiang {U.S. Pat. Nos.6,686,035; 7,223,473; 7,919,177}, Wyndham {WO 2008/103423}, or a POSused in Example 4.

Example 37

The process of Examples 28-36 is modified to replace a part of all ofthe alkoxysilane used with one or more of the following metal oxideprecursors (but not limited to): the oxide, hydroxide, ethoxide,methoxide, propoxide, isopropoxide, butoxide, sec-butoxide,tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide,2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate,nitrate, chlorides, and mixtures thereof of titanium, zirconium, iron,copper, niobium, cobalt, cerium or aluminum. Advantageously, the metaloxide precursors are methyl titanium triisopropoxide, methyl titaniumtriphenoxide, titanium allylacetoacetatetriisopropoxide, titaniummethacrylate triisopropoxide, titanium methacryloxyethylacetoacetatetriisopropoxide, pentamethylcyclopentadienyl titanium trimethoxide,pentamethylcyclopentadienyl titanium trichloride, and zirconiummethacryloxyethylacetoacetate tri-n-propoxide.

Example 38

The process of Examples 28-37 is modified to include incorporation ofone or more nanoparticles within the superficially porous layer,including (but not limited to) nanoparticles listed in Example 10.

Example 39

The process of Examples 28-38 is modified to add or replace part or allof the ionic and or non-ionic surfactants with one or more polyectrolyteor polymers detailed in Examples 21 or 22.

Example 40

The surfactants and or polymers used in select products from Examples28-39 are removed by extraction in a 1-2 M solution of hydrochloric acidin methanol, ethanol or acetone, at elevated temperatures (30-90° C.)for 1-20 hours. Products are isolated on isolated on 0.5 m filtrationpaper and washed consecutively with copious amounts of water andmethanol (HPLC grade, J. T. Baker, Phillipsburgh, N.J.). This processcan be repeated 1-3 times to further remove surfactants and or polymersfrom these particles. Products are dried at 80° C. under vacuum for 16hours and are submitted for carbon, CP-MAS NMR, SEM, and nitrogensorption analysis. For products that contain hybrid content in the shellor porous layer, carbon content is present in the product.Identification of the hybrid product species is made using ¹³C and ²⁹SiCP-MAS NMR spectroscopy. The specific surface areas (SSA) and specificpore volumes (SPV) of these materials are increased with respect to thecore materials used in these reactions. Products prepared by thisapproach are free flowing. Any agglomerated materials can be removedthrough grinding or classification.

Example 41

The surfactants and or polymers used in select products from Examples28-40 are removed by ozonolysis in water at low to moderate temperatures(0-30° C.) for 1-20 hours. Products are isolated on isolated on 0.5 μmfiltration paper and washed consecutively with copious amounts of waterand methanol (HPLC grade, J. T. Baker, Phillipsburgh, N.J.). Thisprocess can be repeated 1-3 times to further remove surfactants and orpolymers from these particles. This process can be combined with an acidextraction approach detailed in Example 40. Products are dried at 80° C.under vacuum for 16 hours and are submitted for carbon, CP-MAS NMR, SEM,and nitrogen sorption analysis. For products that contain hybrid contentin the shell or porous layer, carbon content is present in the product.Identification of the hybrid product species is made using ¹³C and ²⁹SiCP-MAS NMR spectroscopy. The specific surface areas (SSA) and specificpore volumes (SPV) of these materials are increased with respect to thecore materials used in these reactions. Products prepared by thisapproach are free flowing. Any agglomerated materials can be removedthrough grinding or classification.

Example 42

The surfactants and or polymers used in select products from Examples28-41 are removed by 500° C. (10-20 hours) is employed. To furtherstrengthen these superficially porous materials, increased thermaltreatment at 825-1,000° C. in air for 10-20 hours is employed. Productsprepared by this approach are free flowing. Any agglomerated materialscan be removed through grinding or classification.

The specific surface areas (SSA) and specific pore volumes (SPV) ofthese materials are increased with respect to the core materials used inthese reactions. While materials prepared by this process are freeflowing superficially porous particles, the thermal treatments stepsremove all carbon content from these materials. Expected improvement inchemical stability of a hybrid superficially porous material inchromatographic applications is not realized by this approach.

Example 43

When the superficially porous materials of Examples 28-41 containarylene-bridged hybrids, the surfactants and or polymers used in selectproducts from Examples 28-41 are removed by 390-490° C. (10-20 hours) inair or under a nitrogen atmosphere. Products are submitted for carbon,CP-MAS NMR, SEM, and nitrogen sorption analysis. For products thatcontain hybrid content in the shell or porous layer, carbon content ispresent in the product. Identification of the hybrid product species ismade using ¹³C and ²⁹Si CP-MAS NMR spectroscopy. The specific surfaceareas (SSA) and specific pore volumes (SPV) of these materials areincreased with respect to the core materials used in these reactions.Products prepared by this approach are free flowing. Any agglomeratedmaterials can be removed through grinding or classification.

Example 44

To improve pore diameter and further strengthen select materials fromExamples 28-43, hydrothermal treatment methods of Jiang {U.S. Pat. Nos.6,686,035; 7,223,473; 7,919,177} or Wyndham {WO 2008/103423} areemployed. Alternatively, when a material from Examples 28-39 are usedthat have a surfactant or polymer additive, hydrothermal treatments areused to improve pore diameter. Alternatively a surrounding materialmethod described by Wyndham {WO 2010/141426} can be used to strengthenthese superficially porous materials. The surrounding material method isof particular importance when a hybrid inorganic/organic surroundingmaterial is used on the silica superficially porous layer. In thisinstance, the hybrid inorganic/organic surrounding material reduces theporosity. Such materials have improved chemical stability overcommercially available silica superficially porous particles. When thesurrounding material contains nanoparticles, including (but not limitedto) nanodiamonds—as noted in Examples 12 and 13 of Wyndham {WO2010/141426}—improvements in thermal conductivity can be achieved.Products, after surfactant or polymer removal, have pore diametersbetween 60 Å and 350 Å.

Example 45

A series of superficially porous materials were prepared following amulti-step process: (1) Stöber seeds preparation using tetraethoxysilane(TEOS); (2) core growth using TEOS; (3) hybrid layer growth using amixture of TEOS and octadecyltrimethoxysilane (C₁₈TMOS); (4)classification to remove fines; (5) calcination to introduce porosity;(6) pore processing steps; (7) re-calcination to improve mechanicalstrength; (8) rehydroxylation; and (9) surface bonding.

The seeds were prepared by a modified Stöber process. Uniform sizedsilica can be prepared (0.1-2.0 μm) depending on the concentration ofTEOS, composition of the hydrolysis solution, temperatures, and mixing.In current studies, TEOS addition rate was fixed at 0.044 g/mL andhydrolysis solution consisted of ethanol, water and 30% ammoniumhydroxide solution at volume ratio of 80/14/7, respectively. Increasedmixing levels during seed formation resulted in higher content ofaggregates. Optimal mixing conditions were determined to be initialvigorous shaking for 15 seconds before maintaining the reactionunstirred. This approach resulted in less than 5 wt % aggregates.

The cores were further grown with concurrent additions of TEOS andhydrolysis solution (ethanol, waters, and ammonium hydroxide).Additional hydrolysis solution was added to prevent reseeding andaggregation/agglomeration events. Solvent conditions were optimized byexploring ternary phase diagrams to ensure the TEOS was miscible in theaqueous ethanol mixture. Typical addition rates of TEOS and thehydrolysis solution were set at 0.125 mL/min and 1 mL/min, respectively,and the reaction temperature was 50° C. Core size was verified usinglight scattering, Coulter Counter, or SEM.

Upon achieving the desired core size, the TEOS reservoir was switched toa mixture of C₁₈TMOS and TEOS to grow a hybrid layer on the coreparticles. Molar ratios of C₁₈TMOS/TEOS varied from ¼ to 1/9.Advantageous molar ratios are from ¼ to ⅙. Due to differing solubilityof C₁₈TMOS and TEOS the relative addition rates of silanes andhydrolysis solution were adjusted to ensure miscibility. Conditions werebased on the ternary phase diagrams of C₁₈TMOS/TEOS mixtures, water andethanol. The process was monitored by light scattering, Coulter Counter,and SEM. Table 11 details experiments performed in ethanol/water/30%ammonium hydroxide (80/14/7 v/v/v). Table 12 details experiments withvaried hydrolysis solutions.

TABLE 11 Target Target Core Coating Hydrolysis Molar Ratio Silane SizeThickness Temp Solution C₁₈TMOS/ (mL/ Product (μm) (μm) (° C.) (mL/min)TEOS min) 45a 0.8 0.20 50 1.00 1/9 0.123 45b 1.0 0.35 50 1.00 1/9 0.11945c 1.0 0.35 60 1.00 1/9 0.116 45d 1.0 0.35 40 1.00 1/9 0.125 45e 1.00.35 21 1.00 1/9 0.143 45f 1.0 0.35 50 1.00 1/6 0.126 45g 1.0 0.35 601.00 1/6 0.132 45h 1.0 0.35 50 1.26 1/6 0.150 45i 1.0 0.35 50 1.00 1/40.135 45j 1.0 0.35 60 1.00 1/4 0.135 45k 1.0 0.35 50 2.00 1/4 0.132 45l1.0 0.35 60 2.00 1/4 0.140 45m 1.0 0.35 40 2.00 1/4 0.124

TABLE 12 Hydrolysis Solution Volume Ratio Hydrolysis Molar Ratio TempEthanol/ Solution C₁₈TMOS/ Silane Product (° C.) Water/NH₄OH (mL/min)TEOS (mL/min) 45n 21  74/10/3 1.00 1/9 0.125 45o 50  74/10/3 1.00 1/90.125 45p 50 240/52/31 1.00 1/9 0.125 45q 50 240/52/11 1.00 1/9 0.12545r 50 240/32/31 1.00 1/9 0.125 45s 50 240/32/11 1.00 1/9 0.125

Classification was performed, if needed, to remove fines, aggregatesand/or agglomerates. A variety of classification techniques (e.g.,sedimentation, elutriation, and centrifugation) can be used to for thisseparation.

Materials were calcined at 500° C. (1° C./min and held at temperaturefor 12 hours) in air to remove the organic groups and introduceporosity. Products prepared using a 1/9 molar ratio of C₁₈TMOS/TEOS hada SSA between 298-337 m²/g; SPV between 0.20-0.23 cm³/g; and an APDbetween 25-27 Å. Products prepared using a 1/4 molar ratio ofC₁₈TMOS/TEOS had a SSA between 505-508 m²/g; SPV between 0.38-0.41cm³/g; and an APD between 27-28 Å. These APD are too small to be usefulin most HPLC and UPLC applications.

In order to enlarge the pore diameter, a variety of pore processingsteps were explored, detailed in Table 13. Process B allowed for thelargest increase in pore diameter (APD=126-272 Å) when the temperaturewas between 150-200° C. At temperatures between 60-100° C. smallerchanges pore diameters were achieved (APD=27-47 Å). Process A allowedfor a noticeably lower increases in pore diameter (APD=37-94 Å at100-150° C.). Process C allowed for increases in pore volume (SPV) to beachieved (˜0.1 cm³/g) along with small increases in APD (<50 Å). ProcessA or B was also used after Process C to further increase pore diameter.Results for process C were very dependent on the lot, purity, andconcentration of the ammonium bifluoride as well as reaction time. Italso appears this increase in porosity came at the expense of mechanicalstrength. Alternatively, increased porosity was achieved throughmodification of the molar ratio in step 3. An advantageous molar ratioof C₁₈TMOS/TEOS is ¼. Optimal pore processing was achieved usingalkaline hydrothermal treatments at pH 8 (e.g., Process B). Table 14provides details on selected prototypes. Alternative modifications usingother pore modification processes can be performed [U.S. Pat. No.7,223,473; EP2181069; WO2006106493; US publication 20080269368; Chem.Commun., 2007, 1172; Chem Commun, 2007, 111 (3), 1093; Solid StateScience, 2003, 5, 1303; Coll. Surf A, 2003, 229, 1].

TABLE 13 Process Temperature Time Type Description Additives (° C.) (h)A Hydrothermal Treatment 0.2M ammonia acetate/acetic 60-200 20 with pHcontrol (pH 5) B Hydrothermal Treatment 0.2M TRIS (pH 8) 60-200 20 withpH control C Treatment with Ammonium biflouride (0.3-1.0 g 21-50  4-20Ammonium Bifluoride per g silica)

TABLE 14 Process Temp SSA SPV APD Product Type (° C.) (m²/g) (cm³/g) (Å)45t A 100 263 0.33 43 45u B 100 119 0.30 96 45v B 125 70 0.30 164 45w B155 43 0.26 237 45x B 100 107 0.28 99 45y B 200 18 0.10 273

In order to increase the mechanical strength of these materials for usein HPLC and UPLC, a second calcination step was performed at 800° C. (1°C./min then held at temperature for 12 hours). In order to prepare thesematerials for surface modification a rehydroxylation reaction wasperformed in dilute hydrofluoric acid. Particle size and polydispersitywere measured using Coulter Counter or light scattering. As shown inFIG. 7, particle morphology was confirmed to be spherical and freeflowing by SEM. Evaluation of coating thickness and uniformity wasdetermined using FIB/SEM.

Surface bondings were performed on these materials using standardprocedures using octadecyltrichlorosilane (ODTCS) oroctadecyldimethylchlorosilane (ODDMCS). Materials were further endcappedusing monofunctional chlorosilanes using standard protocols. Prototypesdata is provided in Table 15. Surface coverage was determined bydifference in % C data before and after surface modification. Productswere further packed into chromatographic columns and evaluated forperformance (e.g., van Deemter analysis).

TABLE 15 Unbonded Data dp SSA SPV APD C₁₈-coverage Product (μm) (m²/g)(cc/g) (Å) Bonding (μmol/m²) 45z 1.25 88 0.31 128 ODDMCS 1.85 45aa 1.75105 0.25 83 ODDMCS 2.75 45ab 1.65 95 0.24 95 ODDMCS 2.97 45ac 1.74 930.23 92 ODDMCS 2.53 45ad 1.74 96 0.24 95 ODTCS 2.53 45ae 1.53 97 0.26 97ODTCS 2.35

Example 46

Example 45 (steps 1-4) is modified to include the precursor or productmaterials from Examples 1-3, or 5-20. Included in this are spherical,irregular, rod-shaped and toroid-shaped materials. Included in this are0.5-1.9 μm cores that are hybrid, diamond, magnetite, coated diamond, orcoated magnetite. A further modification is not to include steps 5-9.

Example 47

The process of Examples 45-46 is modified to replace a part of all ofthe alkoxysilane used with one or more of the following silanes (but notlimited to) listed in Example 16 and 19, Jiang {U.S. Pat. Nos.6,686,035; 7,223,473; 7,919,177}, Wyndham {WO 2008/103423}, or a POSused in Example 4. A further modification is not to include steps 5-9 ofExample 45.

Example 48

The process of Examples 45-47 is modified to replace a part of all ofthe alkoxysilane used with one or more of the following metal oxideprecursors (but not limited to) listed in Example 37. A furthermodification is not to include steps 5-9 of Example 45.

Example 49

The process of Examples 45-48 is modified to include incorporation ofone or more nanoparticles within the superficially porous layer,including (but not limited to) nanoparticles listed in Example 10. Afurther modification is not to include steps 5-9 of Example 45.

Example 50

To a clean round bottom flask, equipped with a stir bar, thermometer andcondenser was added tetraethoxysilane (Gelest, Morrisville, Pa.) and oneequivalent of octadecanol, dodecanol, octanol, 2-ethoxyethanol, or3-ethyl-3-pentanol (all alcohols were from Aldrich, Milwaukee, Wis.). Acatalytic amount of p-toluene sulfonic acid was added, and the solutionwas stirred and heated overnight at 90° C. under nitrogen. Ethanolgenerated in this process was removed using a rotovap with regularvacuum. The product alkoxysilane was separated by vacuum distillation (2mm Hg) to yield separate products having the following formula;(CH₃CH₂O)_(4-v)Si(OR*)_(v)  (Formula XXb)wherein

R* was the corresponding octadecyl, dodecyl, octyl, 2-ethoxyethyl, or3-ethyl-3-pentyl group,

v was an integer equal to 1-4,

The monoderivatized product (v=1, R*=octadecyl, dodecyl, octyl,2-ethoxyethyl) were isolated in 290% purity by gas chromatography.

Example 51

The process of Examples 28-39, 45-49 is modified to employ a threecomponent alkoxysilane mixture to form a superficially porous layer offormula XX.(D)_(d)(E)_(c)(F)_(f)  (Formula XX)wherein,d+e+f=1,

D is an inorganic component upon initial condensation. Suitableprecursors include (but are not limited to) the oxide, hydroxide,ethoxide, methoxide, propoxide, isopropoxide, butoxide, sec-butoxide,tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide,2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate,nitrate, chlorides, and mixtures thereof of silicon, titanium,zirconium, or aluminum. Advantageously, the precursors aretetraethoxysilane, tetramethoxysilane, methyl titanium triisopropoxide,methyl titanium triphenoxide, titanium allylacetoacetatetriisopropoxide,titanium methacrylate triisopropoxide, titaniummethacryloxyethylacetoacetate triisopropoxide,pentamethylcyclopentadienyl titanium trimethoxide,pentamethylcyclopentadienyl titanium trichloride, and zirconiummethacryloxyethylacetoacetate tri-n-propoxide.

E is a hybrid component upon initial condensation. Suitable precursorsinclude (but are not limited to) alkoxysilanes listed in Example 16 and19, Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} or Wyndham{WO 2008/103423}. Advantageously, E is 1,2-bis(triethoxysilyl)ethane,1,2-bis(trimethoxysilyl)ethane, 1,4-bis(triethoxysilyl)benzene,1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene,1,3-bis(trimethoxysilyl)benzene, 1,3,5-tris(triethoxysilyl)benzene,1,3,5-tris(trimethoxysilyl)benzene, andbis(4-triethoxysilylphenyl)diethoxysilane.

F is a hybrid component upon initial condensation that can be furtherreacted to increase the porosity of the superficially porous layer.Suitable precursors include (but are not limited to) an alkoxysilanefrom Example 50, phenyltrimethoxysilane, phenyltriethoxysilane,acetyloxyethyltrimethoxysilane; acetyloxyethyltriethoxysilane;chloroethyltriethoxysilane; chloroethyltrimethoxysilane;methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane;fluorotriethoxysilane; fluorotrimethoxysilane or silanes reported byCorriu, R. J. P. {Adv. Mater, 2000, 12, 13, 989}. Reactions used toincrease porosity include protodesilylation, deprotection, thermaltreatment <500° C., oxidation or decomposition. Products employingalkoxysilanes from Example 50 can result in products with increasedporosity layers through acid extraction (as detailed in Example 40) orozonolysis (as detailed in Example 41). The resulting reacted materialmay include a hybrid group or silica.

Example 52

Example 51 is modified to have a two component initially condensedformula (d=0). When F includes a silane from Example 50 the produce isreacted by repeated acid extraction (as detailed in Example 40) tocreate a superficially porous layer.

Example 53

Selected materials from Examples 45-49 and 51-52 are further processedfollowing the processes described in Examples 40-44. Classification isperformed if needed to improve the particle size distribution, removingany fines or agglomerated materials.

Example 54

Selected precursor and product core materials from Examples 1-3, or 5-20are surface modified with an alkoxysilane that contains a basic group ofequation 1, using the surface modification methods of Jiang {U.S. Pat.Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}.R(CH₂)_(n)Si(Y)_(3-x)(R′)_(x)  (equation 1)

-   where n=1-30, advantageously 2-3;-   x is 0-3; advantageously 0;-   Y represents chlorine, dimethylamino, triflate, methoxy, ethoxy, or    a longer chain alkoxy group;-   R represent a basic group, including (but not limited to) —NH₂,    —N(R′)H, —N(R′)₂, —N(R′)₃ ⁺, —NH(CH₂)_(m)NH₂, —NH(CH₂)_(m)N(R′)H,    —NH(CH₂)_(m)N(R′)₂, —NH(CH₂)_(m)N(R′)₃ ⁺, pyridyl, imidizoyl,    polyamine.-   R′ independently represents an alkyl, branched alkyl, aryl, or    cycloalkyl group;-   m is 2-6.

Example 55

Selected precursor and product core materials from Examples 1-3, or 5-20are surface modified with an alkoxysilane that contains a basic group ofequation 2, using the surface modification methods of Jiang {U.S. Pat.Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423}.A(CH₂)_(n)Si(Y)_(3-x)(R′)_(x)  (equation 2)

-   where n=1-30, advantageously 2-3;-   x is 0-3; advantageously 0;-   Y represents chlorine, dimethylamino, triflate, methoxy, ethoxy, or    a longer chain alkoxy group; A represent an acidic group, including    (but not limited to) a sulfonic acid, carboxylic acid, phosphoric    acid, boronic acid, arylsulfonic acid, arylcarboxylic acid,    arylphosphonic acid, and arylboronic acid.-   R′ independently represents an alkyl, branched alkyl, aryl, or    cycloalkyl group.

Example 56

Selected nanoparticulate materials detailed in Examples 10, 12, 14, 21,22, 25, 26, 27, 37, and 38 are surface modified with an alkoxysilanethat contains a basic group of equation 1 or 2, using the surfacemodification methods of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473;7,919,177} and Wyndham {WO 2008/103423}.

Example 57

Selected surface modified core materials in Example 54 and 55 arereacted with surface modified nanoparticulate materials in Example 56using a modified process detailed in Example 21. In this approach nopolyelectrolyte is used. Solution pH adjusted for optimal porous layerformation. In certain aspects, the solution pH varies between pH 2-7. Incertain aspects, the optimal pH can vary between pH 4.0-6.5. When apositively charged surface modified core material from Example 54 isused, a negatively charged nanoparticulate material from Example 56 isused. When a negatively charged surface modified core material fromExample 55 is used, a positively charged nanoparticulate material fromExample 56 is used.

After workup and isolation this single layered material can be used asis. Alternatively, additional layers can be added. These can be achievedby repeating this layering process using a nanoparticulate material fromExample 56 of opposite charge from the last surface layer. When the lastsurface layer used positively charged nanoparticulate material fromExample 56, the following layer uses a negatively chargednanoparticulate material from Example 56. When the last surface layeruses a negatively charged nanoparticulate material from Example 56, thefollowing layer uses a positively charged nanoparticulate material fromExample 56. This sequence of alternating charge nanoparticulate materialcan be used to form 2-15 layers on the core material. In this approachno polyelectrolyte material used. The type of nanoparticulate materialused can vary between layers or remain the same. For example, a silicalayer can be layered between diamond or magnetite layers by thisapproach.

The specific surface areas (SSA) and specific pore volumes (SPV) ofthese materials are increased with respect to the core materials used inthese reactions. Products prepared by this approach are free flowing.Any agglomerated materials can be removed through grinding orclassification.

To improve pore diameter and further strengthen these superficiallyporous materials of select materials from Examples 40-43, hydrothermaltreatment methods of Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473;7,919,177} or Wyndham {WO 2008/103423} are employed. Alternatively asurrounding material method described by Wyndham {WO 2010/141426} can beused to strengthen these superficially porous materials. The surroundingmaterial method is of particular importance when a hybridinorganic/organic surrounding material is used on the silicasuperficially porous layer. Such materials have improved chemicalstability over commercially available silica superficially porousparticles. When the surrounding material contains nanoparticles,including (but not limited to) nanodiamonds—as noted in Examples 12 and13 of Wyndham {WO 2010/141426}—improvements in thermal conductivity canbe achieved.

Alternatively, products are thermally treated at 700-1,000° C. for 10-40hours to further strengthen these superficially porous materials. Thisthermal treatment is performed in air, under an inert atmosphere, or ina reducing atmosphere depending on compatibility of the additivesemployed. Materials containing diamond or magnetite employ an inert orreducing atmosphere is used to prevent oxidation.

Example 58

The process of 57 is modified to introduce a polyelectrolyte or polymermaterial from Example 21-27. When the last layer used a positivelycharged nanoparticulate material, the following polyelectrolyte orpolymer used is negatively charged. When the last layer used anegatively charged nanoparticulate material, the followingpolyelectrolyte or polymer used is positively charged.

Example 59

The process of 57-58 is modified to introduce layers formed withpolyelectrolyte and layers formed without polyelectrolyte.

Example 60

The process of 57-59 is modified to use charged nanoparticulatematerials that have been charged modified through acid or base washing,or electrostatically. The charge of these nanoparticulate materials canbe monitored through zeta-potential measurements.

Example 61

The process of 57-60 is modified to hybrid core materials that havesurface acid or base groups. Surface acidic groups can be prepare usinghybrid core materials of the type described in Example 1-3 and 5 usingphenyltriethoxysilane, or mercaptopropyltrimethoxysilane. The phenylgroups can be sulfonated by heating in sulfuric acid. The mercaptopropylgroup can be oxidized to sulfopropyl groups using hydrogen peroxide ornitric acid. The use of a protected aminopropyl group in a hybrid corematerial of the type described in Example 1-3 and 5 can be used tocreate surface basic groups. Methyl iodide treatment of these aminogroups can be used to prepare dimethyl and trimethyl aminopropyl groups.

Example 62

The process of 57-61 is modified to use hybrid nanoparticulate materialsthat have surface acid or base groups of the type detailed in Example61.

Example 63

Select materials from Examples 21-43, 45-49, 51-52, and 57-61 arefurther processed following the processes described in Examples 40-44.Classification is performed if needed to improve the particle sizedistribution, removing any fines or agglomerated materials.

Example 64

Select superficially porous materials prepared according to Examples21-43, 45-49, 51-52, and 57-63 are dispersed in a 1 molar hydrochloricacid solution (Aldrich, Milwaukee, Wis.) for 20 h at 90-98° C.Alternatively materials are rehydroxylated in a 10% nitric acidsolution, or dilute hydrofluoric acid (aqueous). Products are isolatedon filter paper (or a magnetic separator) and are washed repeatedly withdeionized water until a neutral pH is achieved, followed by acetone(HPLC grade, J. T. Baker, Phillipsburgh, N.J.).

Materials can be further treated by sedimentation in acetone to removefines material. The products are dried at 80° C. under vacuum for 16 h.Superficially porous materials, prepared by this approach are submittedfor analysis. The specific surface areas (SSA) and specific pore volumes(SPV) of these materials are increased with respect to the corematerials. SPV vary between 0.08-0.45 cm³/g and average pore diametervaries between 60-300 Å. Particle size measurements and SEM analysisindicate the formation of thick superficially porous layer. This porouslayer thickness varies between 0.07-0.53 μm, material average sizevaries between 1.2-15.0 μm, and the product size distribution (90/10ratio) are similar to the size distribution of the core materials. Thesurface roughness of these materials varies from rough to smooth. Roughsurfaces generally formed from sol-based approaches. Smooth surfacesfrom high purity alkoxysilane-based approaches. The product shapegenerally resembles the core materials. For example, when the cores arespherical, products are spherical. When cores are rod-shaped, productsare rod-shaped. The noticeable difference is these products is arounding of rough edges for jagged or flat faced core materials afterthe porous layer is formed.

Example 65

Select spherical superficially porous materials prepared according toExample 64 are reacted with octadecyldimethylchlorosilane following thegeneral process described in Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473;7,919,177} or Wyndham {WO 2008/103423}. These materials are furtherreacted with trimethylchlorosilane following the general processdescribed in Jiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} orWyndham {WO 2008/103423}. Table 16 contains a description of theseC₁₈-bonded materials. Material compositions used the following notation:(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(SiO₂)_(y)

In this table the following abbreviations are used: SM=Smooth Surfaceand RS=Rough Surface.

TABLE 16 Ratio Initial Porous Product Shell Core Core Core LayerParticle Shell Thickness Composition Size ⁹⁰/₁₀ Composition Product SizeThickness to Radius Product (x, y) (μm) ratio (x, y) Surface (μm) (μm)Core 65a 0, 1 1.18 1.1 1, 0 SM 1.80 0.31 0.53 65b 0, 1 1.18 1.1 1, 0 RS1.80 0.31 0.53 65c 0, 1 1.18 1.5 1, 0 SM 1.80 0.31 0.53 65d 0, 1 1.181.5 1, 0 RS 1.80 0.31 0.53 65e 0, 1 1.70 1.1 1, 0 SM 2.60 0.45 0.53 65f0, 1 1.70 1.1 1, 0 RS 2.60 0.45 0.53 65g 0, 1 1.70 1.5 1, 0 SM 2.60 0.450.53 65h 0, 1 1.70 1.5 1, 0 RS 2.60 0.45 0.53 65i 0, 1 1.10 1.1 1, 0 SM1.80 0.35 0.64 65j 0, 1 1.10 1.1 1, 0 RS 1.80 0.35 0.64 65k 0, 1 1.401.1 1, 0 SM 1.80 0.20 0.29 1.40 1.1 1, 0 RS 1.80 0.20 0.29 65m 0, 1 1.181.1 0.5, 0.5 SM 1.80 0.31 0.53 65n 1, 0 1.18 1.1 0.5, 0.5 SM 1.80 0.310.53 65o 1, 0 1.18 1.1 0, 1 SM 1.80 0.31 0.53 65p 1, 0 1.18 1.1 1, 0 SM1.80 0.31 0.53 65q 0.5, 0.5 1.18 1.1 0.5, 0.5 SM 1.80 0.31 0.53 65r 0.5,0.5 1.18 1.1 0, 1 SM 1.80 0.31 0.53 65s 0.5, 0.5 1.18 1.1 1, 0 SM 1.800.31 0.53

Products of this process are spherical having differences in particlesize, distribution, surface morphology, shell thickness and composition.Products 65a-65h detail the different final particle size, 90/10 ratio,and surface roughness that can be achieved in this process whilemaintain a comparable ratio of shell thickness to radius of the corematerial (0.53). Products 65i-65l have different ratios of shellthickness to radius of the core material (0.29-0.64), while maintaininga comparable final product particle size. These materials can becompared further with Products 65a and 65b. Products 65m-65s havecomparable particle size, distribution, morphology, shell thickness andratio of shell thickness to radius core as Product 65a, but vary incomposition (0-100% hybrid) in both the core and porous layer.

Example 66

Select superficially porous materials prepared according to Example 64are reacted with octadecyldimethylchlorosilane and trimethylchlorosilanefollowing the process described in Example 65. Table 17 contains adescription of these C₁₈-bonded materials. These products containirregular shaped diamond cores that can be coated with silica. The corematerial before formation of the superficially porous layer has anaverage particle size of 1.18 μm and a 90/10 ratio of 1.4. The productshave an average particle size of 1.80 μm, which have a 0.31 um porouslayer thickness and a ratio of porous layer thickness to core radius of0.53. Porous layers composition uses the following notation:(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(SiO₂)_(y)(nanodiamond)_(z),

In this table the following abbreviations are used: SM=Smooth Surface;and RS=Rough Surface.

Products 66a-66h have differences in coating of the diamond cores,composition of the porous layer and surface roughness. Products 66i-66shave different composition of the porous layer to included nanodiamonds.In this approach nanodiamonds are incorporated within the porous layerin 0.1-16 wt %.

TABLE 17 Porous Layer Core Composition Product Product Coated (x, y, z)Surface 66a Silica 1, 0, 0 SM 66b Silica 1, 0, 0 RS 66c None 1, 0, 0 SM66d None 1, 0, 0 RS 66e Silica 0, 1, 0 SM 66f Silica 0, 1, 0 RS 66g None0, 1, 0 SM 66h None 0, 1, 0 RS 66i Silica 0.25, 0.25, 0.5 RS 66j Silica0.35, 0.35, 0.30 RS 66k Silica 0.45, 0.45, 0.1 RS 66l Silica 0.49, 0.49,0.02 RS 66m Silica 0.5, 0, 0.5 RS 66n Silica 0.7, 0, 0.3 RS 66o Silica0.9, 0.0, 0.1 RS 66p Silica 0.99, 0, 0.01 RS 66q Silica 0, 0.5, 0.5 RS66r Silica 0, 0.7, 0.3 RS 66s Silica 0, 0.9, 0.1 RS

Example 67

Select superficially porous materials prepared according to Example 64are reacted with octadecyldimethylchlorosilane and trimethylchlorosilanefollowing the process described in Example 65. Table 18 contains adescription of these C₁₈-bonded materials. These products contain amagnetite core that has been coated with silica. The silica coatedmagnetite core material has an average particle size of 1.18 μm and a90/10 ratio of 1.1-1.5. The products have an average particle size of1.80 μm, which have a 0.31 um porous layer thickness and a ratio ofporous layer thickness to core radius of 0.53. Porous layers compositionuses the following notation:(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(SiO₂)_(y)(nanodiamond)_(z)

In this table the following abbreviations are used: SM=Smooth Surface;and RS=Rough Surface.

Products 67a-67l have different magnetite core size, coated core 90/10ratio, and surface roughness, while having a comparable porous layercomposition. Products 67m-67t have differences in the hybrid andnanodiamond content of the porous layer.

TABLE 18 Porous Magnetite Layer Size Core^(90/10) Composition ProductProduct (μm) Ratio (x, y, z) Surface 67a 0.2 1.1 1, 0, 0 SM 67b 0.2 1.11, 0, 0 RS 67c 0.5 1.1 1, 0, 0 SM 67d 0.5 1.1 1, 0, 0 RS 67e 1 1.1 1, 0,0 SM 67f 1 1.1 1, 0, 0 RS 67g 0.2 1.5 1, 0, 0 SM 67h 0.2 1.5 1, 0, 0 RS67i 0.5 1.5 1, 0, 0 SM 67j 0.5 1.5 1, 0, 0 RS 67k 1 1.5 1, 0, 0 SM 67l 11.5 1, 0, 0 RM 67m 0.5 1.5 0, 1, 0 RS 67n 0.5 1.5 0.5, 0.5, 0 RS 67o 0.51.5 0.25, 0.25, 0.5 RS 67p 0.5 1.5 0.49, 0.49, 0.02 RS 67q 0.5 1.5 0.5,0, 0.5 RS 67r 0.5 1.5 0.99, 0, 0.01 RS 67s 0.5 1.5 0, 0.7, 0.3 RS 67t0.5 1.5 0, 0.9, 0.1 RS

Example 68

Select superficially porous materials prepared according to Example 64are reacted with octadecyldimethylchlorosilane and trimethylchlorosilanefollowing the process described in Example 65. Table 19 contains adescription of these Cis-bonded materials. These products contain rodshaped core materials. Rod shaped cores are described with a length towidth notation. Material composition uses the following notation:(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(SiO₂)_(y)(nanodiamond)_(z)

In this table the following abbreviations are used: SM=Smooth Surface;and RS=Rough Surface; CSD=Cross Sectional Diameter; and CCSR=Core CrossSectional Radius.

Product 68a-l have changes in average core rod length (1-3 μm) andaverage core rod cross sectional diameter (CSD, 1-2 μm) and surfaceroughness, while having a comparable ratio of shell thickness to corerod cross sectional radius (CCSR). Products 68m-68p have changes inshell thickness to cross sectional radius and surface roughness, whilehaving comparable core rod length and core rod CSD. These products canbe compared with 68a-b. Products 68q-ac have changes in composition ofthe core rod and porous layer, while other parameters are comparable toProduct 68b.

TABLE 19 Initial Initial Porous Ratio Core Core Core Layer ProductProduct Shell Shell Composition length CSD Composition Product lengthCSD Thickness Thickness Product (x, y, z) (μm) (μm) (x, y, z) Surface(μm) (μm) (μm) to CCSR 68a 0, 1, 0 3 1 1, 0, 0 SM 3.53 1.53 0.27 0.5368b 0, 1, 0 3 1 1, 0, 0 RS 3.53 1.53 0.27 0.53 68c 0, 1, 0 3 2 1, 0, 0RS 4.06 3.06 0.53 0.53 68d 0, 1, 0 3 1 1, 0, 0 RS 3.53 1.53 0.27 0.5368e 0, 1, 0 3 1.5 1, 0, 0 RS 3.80 2.30 0.40 0.53 68f 0, 1, 0 3 2 1, 0, 0RS 4.06 3.06 0.53 0.53 68g 0, 1, 0 2 1 1, 0, 0 RS 2.53 1.53 0.27 0.5368h 0, 1, 0 2 1.5 1, 0, 0 RS 2.80 2.30 0.40 0.53 68i 0, 1, 0 2 2 1, 0, 0RS 3.06 3.06 0.53 0.53 68j 0, 1, 0 1 1 1, 0, 0 RS 1.53 1.53 0.27 0.5368k 0, 1, 0 1 1.5 1, 0, 0 RS 1.80 2.30 0.40 0.53 68l 0, 1, 0 1 2 1, 0, 0RS 2.06 3.06 0.53 0.53 68m 0, 1, 0 3 1 1, 0, 0 SM 3.30 1.30 0.15 0.3068n 0, 1, 0 3 1 1, 0, 0 RS 3.30 1.30 0.15 0.30 68o 0, 1, 0 3 1 1, 0, 0SM 3.60 1.60 0.30 0.60 68p 0, 1, 0 3 1 1, 0, 0 RS 3.60 1.60 0.30 0.6068q 0, 1, 0 3 1 0, 1, 0 RS 3.53 1.53 0.27 0.53 68r 0, 1, 0 3 1 0.5, 0.5,0 RS 3.53 1.53 0.27 0.53 68s 0, 1, 0 3 1 0.25, 0.25, 0.5 RS 3.53 1.530.27 0.53 68t 0, 1, 0 3 1 0.5, 0, 0.5 RS 3.53 1.53 0.27 0.53 68u 0, 1, 03 1 0, 0.7, 0.3 RS 3.53 1.53 0.27 0.53 68v 0.5, 0.5, 0 3 1 1, 0, 0 RS3.53 1.53 0.27 0.53 68w 0.5, 0.5, 0 3 1 0, 1, 0 RS 3.53 1.53 0.27 0.5368x 0.5, 0.5, 0 3 1 0.5, 0.5, 0 RS 3.53 1.53 0.27 0.53 68y 1, 0, 0 3 11, 0, 0 RS 3.53 1.53 0.27 0.53 68z 1, 0, 0 3 1 0, 1, 0 RS 3.53 1.53 0.270.53 68aa 1, 0, 0 3 1 0.5, 0.5, 0 RS 3.53 1.53 0.27 0.53 68ab 0, 0.7,0.3 3 1 1, 0, 0 RS 3.53 1.53 0.27 0.53 68ac 0, 0.7, 0.3 3 1 0, 1, 0 RS3.53 1.53 0.27 0.53 68ad 0, 0.7, 0.3 3 1 0.5, 0.5, 0 RS 3.53 1.53 0.270.53 68ac 0, 0.7, 0.3 3 1 0, 0.7, 0.3 RS 3.53 1.53 0.27 0.53

Example 69

Select superficially porous materials prepared according to Example 64are reacted with octadecyldimethylchlorosilane and trimethylchlorosilanefollowing the process described in Example 65. Table 20 contains datafor of these C₁₈-bonded materials. These cores have toroid shaped ironoxide, silica, hybrid, or polymeric core materials. Alternatively thesecores are coated with silica. Toroid shaped core materials are describedas an outer diameter (OD), and inner diameter (ID) of open volume, andcross sectional diameter (CSD=0.5(OD-ID)) of material. Materialcomposition uses the following notation:(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(SiO₂)_(y)(nanodiamond)_(z)

In this table the following abbreviations are used: SM=Smooth Surface;and RS=Rough Surface; OD=outer diameter; ID=Inner Diameter; CSD=CrossSectional Diameter; and CCSR=Core Cross Sectional Radius.

Product 69a-g have changes in average product OD (1.63-8.06 μm), averagecore OD (1.5-7 μm) and core CSD (0.5-2 μm), while having a comparableratio of shell thickness to core cross sectional radius (CCSR, 0.53).Products 69h-k have changes in ratio of average shell thickness to CCSR(0.3-0.6) and surface roughness, while having comparable average core ODand average core CSD. These products can be compared with 69d. Products69l-p have changes in composition of the porous layer, while otherparameters are comparable to Product 69d.

TABLE 20 Initial Initial Porous Ratio Core Core Layer Product ProductShell Shell OD CSD Composition Product OD ID Thickness Thickness Product(μm) (μm) (x, y, z) Surface (μm) (μm) (μm) to CCSR 69a 7.0 2.00 1, 0, 0SM 8.06 1.94 0.53 0.53 69b 5.0 1.58 1, 0, 0 SM 5.84 1.00 0.42 0.53 69c5.0 1.00 1, 0, 0 SM 5.53 2.47 0.27 0.53 69d 3.0 0.79 1, 0, 0 SM 3.421.00 0.21 0.53 69e 3.0 0.50 1, 0, 0 SM 3.27 1.74 0.13 0.53 69f 2.0 0.501, 0, 0 SM 2.27 0.74 0.13 0.53 69g 1.5 0.25 1, 0, 0 SM 1.63 0.87 0.070.53 69h 3.0 0.79 1, 0, 0 SM 3.24 1.18 0.12 0.30 69i 3.0 0.79 1, 0, 0 RS3.24 1.18 0.12 0.30 69j 3.0 0.79 1, 0, 0 SM 3.47 0.95 0.24 0.60 69k 3.00.79 1, 0, 0 RS 3.47 0.95 0.24 0.60 69l 3.0 0.79 0, 1, 0 SM 3.42 1.000.21 0.53 69m 3.0 0.79 0.5, 0.5, 0 SM 3.42 1.00 0.21 0.53 69n 3.0 0.790.25, 0.25, SM 3.42 1.00 0.21 0.53 0.5 69o 3.0 0.79 0.5, 0, 0.5 SM 3.421.00 0.21 0.53 69p 3.0 0.79 0, 0.7, 0.3 SM 3.42 1.00 0.21 0.53

Example 70

Select superficially porous materials prepared according to Example 64are reacted with octadecyldimethylchlorosilane and trimethylchlorosilanefollowing the process described in Example 65. Table 22 contains data ofthese Cis-bonded materials. These products contain composite sphericalcore particles that have an average particle size of 1.18 m and a 90/10ratio of 1.4. Porous layers composition uses the following notation:(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x)(SiO₂)_(y)(nanodiamond)_(z)(nanotitania)_(1−(x+y+z))These products have an average particle size of 1.80 μm, which have a0.31 μm porous layer thickness and a ratio of porous layer thickness tocore radius of 0.53.

TABLE 22 Porous Layer nanoparticles Composition Product in silica (x, y,z) 70a diamond 1, 0, 0 70b diamond 0, 1, 0 70c diamond 0.5, 0.5, 0 70ddiamond 0.25, 0.25, 0.5 70e diamond 0, 0.3, 0.3 70f diamond 0.5, 0, 070g diamond 0.25, 0.25, 0 70h diamond 0.25, 0.25, 0.25 70i magnetite 1,0, 0 70j magnetite 0, 1, 0 70k magnetite 0.5, 0.5, 0 70l magnetite 0.25,0.25, 0.5 70n magnetite 0, 0.3, 0.3 70o titania 1, 0, 0 70p titania 0,1, 0 70q titania 0.5, 0.5, 0 70r titania 0.25, 0.25, 0.5 70s titania 0,0.3, 0.3 70t diamond and 1, 0, 0 magnetite 70u diamond and 0, 1, 0magnetite 70v diamond and 0.5, 0.5, 0 magnetite 70w diamond and 0.25,0.25, 0.5 magnetite 70x diamond and 0, 0.3, 0.3 magnetite 70y diamondand titania 1, 0, 0 70z diamond and titania 0, 1, 0 70aa diamond andtitania 0.5, 0.5, 0 70ab diamond and titania 0.25, 0.25, 0.5 70acdiamond and titania 0, 0.3, 0.3

Example 71

Select materials prepared according to Example 64 and C₁₈-bondedmaterials prepared according to Example 65-70 are packed into 2.1×100 mmchromatographic columns using a slurry packing technique. Theperformance of these materials is evaluated using an ACQUITY UPLC®System and an ACQUITY UPLC® Tunable UV detector. Empower 2Chromatography Data Software is used for data collection and analysis.Columns are evaluated under a series of different tests described inJiang {U.S. Pat. Nos. 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO2008/103423; WO 2011/017418}, including isocratic reversed-phase (pH 3and pH 7), gradient separations, and accelerated stability tests withhigh pH mobile phases.

Example 72

Mixtures of spherical and rod shaped C₁₈-bonded materials preparedaccording to Examples 65 and 68 are packed into 2.1×100 mmchromatographic columns using a slurry packing technique. The weightpercent of rod-shaped materials varies from 1-95 wt %. The performanceof these materials is evaluated using an ACQUITY UPLC® System and anACQUITY UPLC® Tunable UV detector. Empower 2 Chromatography DataSoftware is used for data collection and analysis. Reductions and columnpressure and an increase in interstitial porosity and interstitialfraction is determined for columns containing increased content ofrod-shaped materials. Interstitial fraction is well known in the art andcan be determined by a number of known methods including (but notlimited to) inverse size exclusion chromatography.

Example 73

Following a modified process of Example 21, to a mixture of 0.5-1.0 μmdiamond particles (5 g, Mypodiamond, Smithfield, Pa.) dispersed indeionized water (45 g) was added a 0.5 wt % aqueous solution ofpoly(diallyldimethylammonium chloride) (225 g, MW=100,000-200,000,Aldrich, Milwaukee, Wis.). The mixture was stirred for 10 minutes andthe treated particles were collected by centrifugation. The particleswere washed by four-fold repeated dispersion in deionized water (250mL), followed by centrifugation. The particles were redispersed indeionized water (150 mL) before addition of a 10 wt % aqueous solutionof 59 nm silica sols (50 g, Nexsil 85NH4, Nyacol Nano Technologies,Ashland, Mass., pH was adjusted to 2.98 using dilute nitric acid). Themixture was stirred for 15 minutes before collecting the particles bycentrifugation. The particles were washed by five-fold repeateddispersion in deionized water (250 mL), followed by centrifugation(Product 73L1).

The particles were dispersed in deionized water (100 g) before additionof a 0.5 wt % aqueous solution of poly(diallyldimethylammonium chloride)(225 g, MW=100,000-200,000, Aldrich, Milwaukee, Wis.). The mixture wasstirred for 10 minutes and the treated particles were collected bycentrifugation. The particles were washed by four-fold repeateddispersion in deionized water (250 mL), followed by centrifugation. Theparticles were redispersed in deionized water (150 mL) before additionof a 10 wt % aqueous solution of 59 nm silica sols (50 g, Nexsil 85NH4,Nyacol Nano Technologies, Ashland, Mass., pH was adjusted to 2.98 usingdilute nitric acid). The mixture was stirred for 15 minutes beforecollecting the particles by centrifugation. The particles were washed byfive-fold repeated dispersion in deionized water (250 mL), followed bycentrifugation (Product 73L2).

Aqueous samples were taken and air dried for SEM analysis (FIG. 4).Final product—was dried using lyophilization. Products prepared in thismanner have both silica sols and polyelectrolyte on the core diamondmaterial. As shown in FIG. 4 there is a clear difference in productmorphology and surface roughness after a single layer of silica is addedto the diamond cores.

Example 74

A superficially porous silica layer was formed on the product 18a fromExample 18 using a modified process of Example 21. Silica coatedmagnetic cores (18a, 1.2 μm, 20 mg) were resuspended in a 0.5 wt %aqueous solution of polyethylenimine (1.0 mL, PEI, MW=2,000, Aldrich).This mixture was then mixed on a rotator for 10 minutes. Materials wereisolated using a magnetic separator and were washed four times withdeionized water (3.0 mL, MilliQ) before being resuspended in deionizedwater (0.6 mL). A 10 wt % aqueous solution of 59 nm silica sols (200 μl,Nexsil 85NH4, Nyacol Nano Technologies, Ashland, Mass., pH adjusted to3.48) was then added. The mixture was rotated for 15 minutes, beforeisolating the product using a magnetic separator. The product was washedfive times with deionized water (3.0 mL). The product (74L1) wasisolated using a magnetic separator.

This process was repeated twice more to produce products a second(product 74L2) and third layer (product 74L3). The final product was airdried on a Nucleopore filter (0.2 μm, Whatman). SEM analysis (FIG. 5)shows a final particle with a rough surface, having an average particlesize of 1.4 μm. This product has a 0.1 μm thick porous shell on the topof a 0.35 μm non-porous silica shell on a 0.5 μm diameter magnetic coreparticle.

Example 75

Products 73L2 and 74L3 are thermally treated under a nitrogen atmosphereat 500° C. and 800-900° C. following the process of Example 21. An inertatmosphere is used to prevent oxidation of the diamond or magnetitecores. Classification is performed to improve the particle sizedistribution and remove any fines or agglomerated materials. Thesematerials are rehydroxylated using the process of Example 64 and arereacted with octadecyldimethylchlorosilane and trimethylchlorosilaneusing the process of Example 65. C₁₈-bonded diamond core superficiallyporous particles (product 75a) and C₁₈-bonded magnetic coresuperficially porous particles (product 75b) are packed into achromatographic device and performance is evaluated.

Example 76

1.26 μm nonporous silica particles (10.4 g), that were previouslythermally treated at 600° C. (10 h) and rehydroxylated using 10% nitricacid (Fisher scientific), were dispersed in 100 mL of solvent(water:anhydrous ethanol 2:1 v/v) by sonicating for 10 minutes.Separately, octadecyltrimethylammonium bromide (3.0 g, C₁₈TAB,Sigma-Aldrich) was dissolved in 100 mL of solvent (water:anhydrousethanol 2:1 v/v). The C₁₈TAB solution was then added into the particlesolution and sonicated for 10 minutes. This solution was labeledsolution A. In a separate beaker of Pluronic P123 (58.0 g,Sigma-Aldrich) was dissolved in 400 mL of solvent (water:anhydrousethanol 2:1 v/v) and was labeled solution B. Solution B was added intosolution A and allowed to continue sonicate for 20 minutes. The mixturewas then transferred into a 1 L round bottom flask and stirred at 750rpm. Ammonium hydroxide solution (30%, J. T. Baker) was added into theflask and allowed to continue stirring for 5 minutes. A 3.3:1 mol ratiomixture of tetraethoxysilane (TEOS, Sigma-Aldrich) and1,2-bis(triethoxysilyl)ethane (BTEE, Gelest) was first diluted withanhydrous ethanol (dilution factor=3) and was added to the flask using aperistaltic pump (ISMATEC, ISM596D equipped with 1/32 inch diameter PTFEtubing from Cole-Palmer) at 50 μL/min. Once all the mixture was addedthe reaction was allowed to continue for 1 h before wash. The wash stepswere performed as detailed in Example 28. This process was repeated twomore times. The volume of the solution was increased to compensate forthe increase in the solids volume maintaining the concentrations of thereagents constant. See Table 23 below for specific reaction conditions.An SEM image of product 76L2 is shown in FIG. 6.

silane particle mixture C₁₈TAB Sol. A P123 Sol. B NH₄OH size SEM ProductLayer (mL) (g) (mL) (g) (mL) (mL) (μm) Comments 76L1 1 6.0 3.0 200 58400 18 1.54 Well dispersed particles No fine particles 76L2 2 7.5 5.0300 92 500 30 1.66 Dispersed particles Small amount of fine particles76L3 3 8.1 6.0 400 115 600 45 1.84 Dispersed particles Small amount offine particles

Example 77

The process of Example 76 was modified using a 1.6:1 mol ratio mixtureof tetraethoxysilane and 1,2-bis(triethoxysilyl)ethane. See Table 24below for specific reaction data. An SEM image of product 77L2 is shownin FIG. 6.

TABLE 24 particle size SEM Product Layer (μm) Comments 77L1 1 1.47 Welldispersed particles No fine particles 77L2 2 1.58 Dispersed particlesSmall amount of fine particles 77L3 3 1.68 Higher amount of fineparticles

Example 78

The process of Example 76 was modified using only1,2-bis(triethoxysilyl)ethane. An SEM image of product 78L2 indicates a1.55 μm average particle size that is highly aggregated and hasincreased quantities of fine particles (<1 μm).

Example 79

Hybrid porous layer, superficially porous particles (3.3 g) preparedfollowing Examples 28-32 were dispersed in a 2 molar solution ofhydrochloric acid in acetone. The mixture was mechanically stirred for18 hours at room temperature. Products were isolated by centrifugation(Forma Scientific Model 5681, 4,000 rpm, 10 min) followed by repeatedwashes with deionized water until the pH was greater than 6, followed bytwo methanol washes. Sonication was used between washes to improveddispersion. Products were dried at 80° C. under vacuum for 16 hours andsubmitted for SEM, and nitrogen sorption analysis. Material data isshown in Table 25. Average particle size was determined by SEM.

TABLE 25 Surface Pore Particle Area Volume Size SSA SPV ProductPrecursor (μm) (m²/g) (cm³/g) 79a 28f 1.43 178 0.09 79b 29c 1.57 2920.17 79c 29d 1.68 400 0.23 79d 32a 1.65 246 0.14 79e 32b 1.61 296 0.17

Example 80

Select materials from Examples 76-78 have surfactants removed by acidextraction following the process of Example 79.

Example 81

Select materials from Examples 79-80 are treated by ozonolysis followingthe process of Example 41, hydrothermally treated following the processof Example 44, and acid treated as detailed in Example 79, andclassification to remove fines and/or agglomerated materials. Thesematerials are reacted with octadecyldimethylchlorosilane andtrimethylchlorosilane using the process of Example 65. These C₁₈-bondedhybrid porous layer superficially porous particles are packed into achromatographic device and performance is evaluated.

Example 82

Select unbounded materials from Examples 63, 64, 75, 79-81 have silanolgroups surface modified following the process of Jiang {U.S. Pat. Nos.6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008/103423} withreagents including (but not limited to) of the type:Z_(a)(R′)_(b)Si—R,where

-   Z=Cl, Br, I, C₁-C₅ alkoxy, dialkylamino or    trifluoromethanesulfonate;-   a and b are each an integer from 0 to 3 provided that a+b=3;-   R′ is a C₁-C₆ straight, cyclic or branched alkyl group, methyl,    ethyl, propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl,    isopentyl, hexyl and cyclohexyl-   R is a functionalizing group selected from the group consisting of    alkyl, alkenyl, alkynyl, aryl, cyano, amino, diol, nitro, ester, a    cation or anion exchange group, a pyridyl group, a    pentafluorophenylalkyl group, an alkyl or aryl group containing an    embedded polar functionality, and a C₁-C₃₀ alkyl group

Advantageous silanol surface modification groups include (but are notlimited to) octyltrichlorosilane, octadecyltrichlorosilane,octyldimethylchlorosilane, phenylhexyltrichlorosilane,n-butyldimethylchlorosilane, tert-butyldimethylchlorosilane,triisopropylchlorosilane, cyanopropyldiisopropylchlorosilane,pentafluorophenylpropyltrichlorosilane, 2-pyridylethyltrimethoxysilane,and octadecyldimethylchloro silane

Alternatively, the materials are surface modified by forming an organiccovalent bond between surface organic groups and the modifying reagent.Alternatively, the materials are surface modified by coating with apolymer. Alternatively, the materials are modified by a combination oforganic group and silanol group modification. Alternatively, thematerials are surface modified by a combination of silanol groupmodification and coating with a polymer. Alternatively, the materialsare surface modified by a combination of organic group modification andcoating with a polymer. Alternatively, the materials are surfacemodified by a combination of organic group modification, silanol groupmodification, and coating with a polymer.

Example 83

Select unbounded materials from Example 45 (products 45t-45x) aremodified with one more or more layers formed using an organosiloxane, amixture of organosiloxane and alkoxysilane, polyorganoalkoxysilanes, ahybrid inorganic/organic surrounding material, or combination thereof.These materials have increased hybrid content near the external particlesurface.

The invention claimed is:
 1. A superficially porous material comprisingsuperficially porous particles, wherein the superficially porousparticles comprise an inorganic/organic hybrid core and one or morelayers of a porous shell material surrounding the inorganic/organichybrid core wherein the inorganic/organic hybrid core has a pore volumeof less than 0.10 cc/g; and wherein the inorganic/organic hybrid corehas the formula:(SiO₂)_(d)/[(R)_(p)(R¹)_(q)SiO_(t)]  (II) wherein, R and R¹ are eachindependently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl; d is 0 to about 30; p and q are eachindependently 0.0 to 3.0, p+q=3.0 and t=0.5.
 2. The superficially porousmaterial of claim 1, wherein the superficially porous material haschromatographically enhancing pore geometry.
 3. The superficially porousmaterial of claim 1, wherein the porous shell material is a porousinorganic/organic hybrid material.
 4. The superficially porous materialof claim 1, wherein the porous shell material is a porous silica.
 5. Thesuperficially porous material of claim 1, wherein the porous shellmaterial is a porous composite material.
 6. The superficially porousmaterial of claim 1, wherein the superficially porous particles includemore than one layer of a porous shell material wherein each layer of theporous shell material is independently selected from a porousinorganic/organic hybrid material of formula (II) according to claim 1,a porous silica, a porous composite material, or mixtures thereof. 7.The superficially porous material of claim 1, wherein the superficiallyporous material has a spherical core morphology, a rod shaped coremorphology, a bent-rod shaped core morphology, a toroid shaped coremorphology, or a dumbbell shaped core morphology.
 8. The superficiallyporous material of claim 1, wherein the inorganic/organic hybrid corehas a particle size of 0.5-10 μm.
 9. The superficially porous materialof claim 1, wherein the superficially porous particles include more thanone layer of a porous shell material, and wherein each layer of porousshell material is independently from 0.05 μm to 5 μm in thickness asmeasured perpendicular to the surface of the inorganic/organic hybridcore.
 10. The superficially porous material of claim 1, wherein thesuperficially porous material has an average particle size between0.8-10.0 μm.
 11. The superficially porous material of claim 1, whereinthe superficially porous material has an average pore diameter of about25-600 Å.
 12. The superficially porous material of claim 1, wherein thesuperficially porous material has an average pore volume of about0.11-0.50 cm³/g.
 13. The superficially porous material of claim 1,wherein pore surface area is between about 10 m²/g and 400 m²/g.
 14. Thesuperficially porous material of claim 1, which has been further surfacemodified.
 15. The superficially porous material of claim 1, which hasbeen further surface modified by: coating with a polymer; coating with apolymer by a combination of organic group and silanol groupmodification; a combination of organic group modification and coatingwith a polymer; a combination of silanol group modification and coatingwith a polymer; formation of an organic covalent bond between an organicgroup of the material and a modifying reagent; or a combination oforganic group modification, silanol group modification and coating witha polymer.
 16. A separations device having a stationary phase comprisingthe superficially porous material of claim
 1. 17. A chromatographiccolumn, comprising a) a column having a cylindrical interior foraccepting a packing material and b) a packed chromatographic bedcomprising the superficially porous material of claim
 1. 18. Achromatographic device, comprising a) an interior channel for acceptinga packing material and b) a packed chromatographic bed comprising thesuperficially porous material of claim
 1. 19. A kit comprising thesuperficially porous material of claim 1, and instructions for use. 20.The superficially porous material of claim 1, wherein each layer of theporous shell material is independently selected from a porousinorganic/organic hybrid material of formula (II) according to claim 1.